NM_005267.5(GJA8):c.201C>G (p.Asp67Glu) AND Cataract 1 multiple types

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 4, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001224560.7

Allele description [Variation Report for NM_005267.5(GJA8):c.201C>G (p.Asp67Glu)]

NM_005267.5(GJA8):c.201C>G (p.Asp67Glu)

Gene:

GJA8:gap junction protein alpha 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.2

Genomic location:

Preferred name:

NM_005267.5(GJA8):c.201C>G (p.Asp67Glu)

HGVS:

NC_000001.11:g.147908156C>G
NG_016242.1:g.10338C>G
NM_005267.5:c.201C>GMANE SELECT
NP_005258.2:p.Asp67Glu
NC_000001.10:g.147380283C>G
NM_005267.4:c.201C>G

Protein change:

D67E

Links:

dbSNP: rs781782991

NCBI 1000 Genomes Browser:

rs781782991

Molecular consequence:

NM_005267.5:c.201C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cataract 1 multiple types
Synonyms:: CATARACT, DUFFY-LINKED; Cataract 1; CATARACT 1, MULTIPLE TYPES, WITH OR WITHOUT MICROCORNEA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007285; MedGen: C1861828; Orphanet: 1377; OMIM: 116200

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LOC101929279 [Homo sapiens]
LOC101929279 [Homo sapiens]
Gene ID:101929279

Gene
MAN2C1 mannosidase alpha class 2C member 1 [Equus caballus]
MAN2C1 mannosidase alpha class 2C member 1 [Equus caballus]
Gene ID:100061610

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001396765	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 4, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23508780, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001396765

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 4, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Whole exome sequencing in dominant cataract identifies a new causative factor, CRYBA2, and a variety of novel alleles in known genes.

Reis LM, Tyler RC, Muheisen S, Raggio V, Salviati L, Han DP, Costakos D, Yonath H, Hall S, Power P, Semina EV.

Hum Genet. 2013 Jul;132(7):761-70. doi: 10.1007/s00439-013-1289-0. Epub 2013 Mar 19.

PubMed [citation]

PMID:: 23508780
PMCID:: PMC3683360

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001396765.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces aspartic acid with glutamic acid at codon 67 of the GJA8 protein (p.Asp67Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with congenital cataracts (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Asp67 amino acid residue in GJA8. Other variant(s) that disrupt this residue have been observed in individuals with GJA8-related conditions (PMID: 23508780), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024

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