NM_001164508.2(NEB):c.20158-6A>G AND Arthrogryposis multiplex congenita 6

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jun 28, 2023
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002250662.3

Allele description [Variation Report for NM_001164508.2(NEB):c.20158-6A>G]

NM_001164508.2(NEB):c.20158-6A>G

Gene:

NEB:nebulin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q23.3

Genomic location:

Preferred name:

NM_001164508.2(NEB):c.20158-6A>G

HGVS:

NC_000002.12:g.151547744T>C
NG_009382.2:g.191744A>G
NM_001164507.2:c.20158-6A>G
NM_001164508.2:c.20158-6A>GMANE SELECT
NM_001271208.2:c.20158-6A>G
NM_004543.5:c.15055-6A>G
LRG_202t1:c.20158-6A>G
LRG_202:g.191744A>G
NC_000002.11:g.152404258T>C
NM_001164508.2:c.20158-6A>G
NM_001271208.1:c.20158-6A>G

Links:

dbSNP: rs1553715636

NCBI 1000 Genomes Browser:

rs1553715636

Molecular consequence:

NM_001164507.2:c.20158-6A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001164508.2:c.20158-6A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001271208.2:c.20158-6A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_004543.5:c.15055-6A>G - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Name:: Arthrogryposis multiplex congenita 6
Identifiers:: MONDO: MONDO:0030281; MedGen: C5543431; OMIM: 619334

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002521786	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004200233	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 28, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002521786

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 22, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004200233

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 28, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV002521786.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Splice region (3-8 bases of the intron) variant: see below. In silico tools predict the variant to alter splicing and produce an abnormal transcript (SpliceAI: 1.00). Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Baylor Genetics, SCV004200233.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 4, 2024

ClinVar

Relating variation to medicine