VCV000333874.31 - ClinVar

NM_006891.4(CRYGD):c.168C>G (p.Tyr56Ter)

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.

(8)

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(3); Likely benign(3)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_006891.4(CRYGD):c.168C>G (p.Tyr56Ter)

Variation ID: 333874 Accession: VCV000333874.31

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q33.3 2: 208124196 (GRCh38) [ NCBI UCSC ] 2: 208988920 (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	Dec 6, 2016	Oct 20, 2024	Aug 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_006891.4:c.168C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_008822.2:p.Tyr56Ter	nonsense
NC_000002.12:g.208124196G>C
NC_000002.11:g.208988920G>C
NG_008039.1:g.5394C>G

Protein change

Y56*

Other names

Canonical SPDI

NC_000002.12:208124195:G:C

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.

0.00359 (C)

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

Trans-Omics for Precision Medicine (TOPMed) 0.00463

Exome Aggregation Consortium (ExAC) 0.00528

The Genome Aggregation Database (gnomAD), exomes 0.00627

1000 Genomes Project 0.00359

Links

ClinGen: CA2077717 dbSNP: rs202233735 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.
CRYGD		-	-	GRCh38 GRCh38 GRCh37	1	120
LOC100507443	-	-	-	GRCh38 GRCh38	-	232

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.
Cataract 4 multiple types	Conflicting interpretations of pathogenicity (3)	criteria provided, conflicting classifications	Jan 1, 2019	RCV000414998.14
Aculeiform cataract	Benign (1)	criteria provided, single submitter	Nov 27, 2023	RCV000859322.8
Joubert syndrome 17	Likely benign (1)	criteria provided, single submitter	-	RCV001258237.2
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Aug 1, 2024	RCV001636930.13
CRYGD-related disorder	Likely benign (1)	no assertion criteria provided	May 22, 2019	RCV003983020.2

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.
Likely benign (Dec 31, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cataract 4 multiple types Affected status: yes Allele origin: germline	Baylor Genetics Accession: SCV000328716.2 First in ClinVar: Jan 13, 2017 Last updated: Sep 21, 2019 Comment: Reclassification of existing record
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Cataract 4 multiple types Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000426673.3 First in ClinVar: Dec 06, 2016 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Joubert syndrome 17 (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard Accession: SCV001435143.1 First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020	Publications: PubMed (2) PubMed: 19390652‚ 22995991 Comment: The heterozygous p.Tyr56Ter variant in CRYGD has been identified in 3 Brazilian relatives from 1 family with cataracts (PMID: 19390652), but has also been identified … (more) The heterozygous p.Tyr56Ter variant in CRYGD has been identified in 3 Brazilian relatives from 1 family with cataracts (PMID: 19390652), but has also been identified in >3% of Latino chromosomes and 4 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal dominant cataracts. (less)
Uncertain significance (Jan 01, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cataract 4 multiple types Affected status: yes Allele origin: unknown	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV001440806.1 First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020
Benign (Nov 27, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Aculeiform cataract Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000644751.7 First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024
Benign (Feb 27, 2020)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001852472.1 First in ClinVar: Sep 12, 2021 Last updated: Sep 12, 2021	Comment: This variant is associated with the following publications: (PMID: 31216405, 28849415, 27959697, 27535533, 19390652, 22995991)
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: SCV004148465.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: CRYGD: BS1, BS2 Number of individuals with the variant: 3
Likely benign (May 22, 2019)	no assertion criteria provided Method: clinical testing	CRYGD-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004796747.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

The heterozygous p.Tyr56Ter variant in CRYGD has been identified in 3 Brazilian relatives from 1 family with cataracts (PMID: 19390652), but has also been identified in >3% of Latino chromosomes and 4 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal dominant cataracts.

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
An informatics approach to analyzing the incidentalome.	Berg JS	Genetics in medicine : official journal of the American College of Medical Genetics	2013	PMID: 22995991
Mutation analysis of CRYAA, CRYGC, and CRYGD associated with autosomal dominant congenital cataract in Brazilian families.	Santana A	Molecular vision	2009	PMID: 19390652

Text-mined citations for rs202233735 ...

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 Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_006891.4(CRYGD):c.168C>G (p.Tyr56Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs202233735 ...