VCV000094334.45 - ClinVar

NM_001130987.2(DYSF):c.605C>A (p.Ala202Glu)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(14)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(6); Likely benign(2)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001130987.2(DYSF):c.605C>A (p.Ala202Glu)

Variation ID: 94334 Accession: VCV000094334.45

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2p13.2 2: 71513767 (GRCh38) [ NCBI UCSC ] 2: 71740897 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 6, 2014	Oct 20, 2024	Aug 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001130987.2:c.605C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001124459.1:p.Ala202Glu	missense
NM_003494.4:c.509C>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003485.1:p.Ala170Glu	missense
NM_001130455.2:c.512C>A	NP_001123927.1:p.Ala171Glu	missense
NM_001130976.2:c.509C>A	NP_001124448.1:p.Ala170Glu	missense
NM_001130977.2:c.509C>A	NP_001124449.1:p.Ala170Glu	missense
NM_001130978.2:c.509C>A	NP_001124450.1:p.Ala170Glu	missense
NM_001130979.2:c.602C>A	NP_001124451.1:p.Ala201Glu	missense
NM_001130980.2:c.602C>A	NP_001124452.1:p.Ala201Glu	missense
NM_001130981.2:c.602C>A	NP_001124453.1:p.Ala201Glu	missense
NM_001130982.2:c.605C>A	NP_001124454.1:p.Ala202Glu	missense
NM_001130983.2:c.512C>A	NP_001124455.1:p.Ala171Glu	missense
NM_001130984.2:c.512C>A	NP_001124456.1:p.Ala171Glu	missense
NM_001130985.2:c.605C>A	NP_001124457.1:p.Ala202Glu	missense
NM_001130986.2:c.512C>A	NP_001124458.1:p.Ala171Glu	missense
NC_000002.12:g.71513767C>A
NC_000002.11:g.71740897C>A
NG_008694.1:g.65145C>A
LRG_845:g.65145C>A
LRG_845t1:c.509C>A	LRG_845p1:p.Ala170Glu
LRG_845t2:c.605C>A	LRG_845p2:p.Ala202Glu
	O75923:p.Ala170Glu

... more HGVS ... less HGVS

Protein change

A170E, A202E, A201E, A171E

Other names

Canonical SPDI

NC_000002.12:71513766:C:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00419 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.00419

1000 Genomes Project 30x 0.00453

Trans-Omics for Precision Medicine (TOPMed) 0.00913

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01038

Links

ClinGen: CA147766 UniProtKB: O75923#VAR_024853 dbSNP: rs34999029 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
DYSF		-	-	GRCh38 GRCh37	4065	4114

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign/Likely benign (6)	criteria provided, multiple submitters, no conflicts	Feb 18, 2022	RCV000080300.33
Qualitative or quantitative defects of dysferlin	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Jan 31, 2024	RCV000531528.25
Autosomal recessive limb-girdle muscular dystrophy type 2B	Benign (1)	no assertion criteria provided	Sep 16, 2020	RCV001273964.9
Miyoshi muscular dystrophy 1	Likely benign (1)	criteria provided, single submitter	May 18, 2021	RCV001449921.10
not provided	Benign (4)	criteria provided, single submitter	Aug 1, 2024	RCV001699034.23

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (May 11, 2017)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000519692.2 First in ClinVar: Mar 08, 2017 Last updated: Apr 09, 2018	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Mar 28, 2013)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000112195.8 First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DYSF Number of individuals with the variant: 3 Sex: mixed
Uncertain significance (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Qualitative or quantitative defects of dysferlin Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001300714.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
Benign (Aug 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV002822663.14 First in ClinVar: Jan 21, 2023 Last updated: Oct 20, 2024	Comment: DYSF: BP4, BS1, BS2 Number of individuals with the variant: 17
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000309695.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jan 13, 2015)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000711689.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: p.Ala202Glu in exon 7 of DYSF: This variant is not expected to have clinical sig nificance because it has been identified in 1.5% (132/8600) of … (more) p.Ala202Glu in exon 7 of DYSF: This variant is not expected to have clinical sig nificance because it has been identified in 1.5% (132/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs34999029). (less) Number of individuals with the variant: 1
Likely benign (May 18, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Miyoshi muscular dystrophy 1 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001653320.1 First in ClinVar: Jun 08, 2021 Last updated: Jun 08, 2021	Sex: mixed
Likely benign (Feb 18, 2022)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002103694.1 First in ClinVar: Mar 12, 2022 Last updated: Mar 12, 2022
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Qualitative or quantitative defects of dysferlin Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000649720.8 First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024
Likely benign (-)	no assertion criteria provided Method: clinical testing	AllHighlyPenetrant (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000151034.2 First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014	Comment: Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more) Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. (less)
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001920321.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001926883.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Limb-girdle muscular dystrophy type 2B Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001457600.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002035786.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021
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Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

Comment:

p.Ala202Glu in exon 7 of DYSF: This variant is not expected to have clinical sig nificance because it has been identified in 1.5% (132/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs34999029).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DYSF	-	-	-	-

Text-mined citations for rs34999029 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_001130987.2(DYSF):c.605C>A (p.Ala202Glu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs34999029 ...