NM_003742.4(ABCB11):c.2538G>T (p.Trp846Cys) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 5, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000734053.7

Allele description [Variation Report for NM_003742.4(ABCB11):c.2538G>T (p.Trp846Cys)]

NM_003742.4(ABCB11):c.2538G>T (p.Trp846Cys)

Gene:

ABCB11:ATP binding cassette subfamily B member 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.1

Genomic location:

Preferred name:

NM_003742.4(ABCB11):c.2538G>T (p.Trp846Cys)

HGVS:

NC_000002.12:g.168944677C>A
NG_007374.2:g.91720G>T
NM_003742.4:c.2538G>TMANE SELECT
NP_003733.2:p.Trp846Cys
LRG_1199t1:c.2538G>T
LRG_1199:g.91720G>T
LRG_1199p1:p.Trp846Cys
NC_000002.11:g.169801187C>A
NG_007374.1:g.91647G>T

Protein change:

W846C

Links:

dbSNP: rs1208988638

NCBI 1000 Genomes Browser:

rs1208988638

Molecular consequence:

NM_003742.4:c.2538G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Vernonia cinerea internal transcribed spacer 1, partial sequence; 5.8S ribosomal...
Vernonia cinerea internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|34369928|gb|AY142953.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000862164	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Uncertain significance (Jun 26, 2018)	germline	clinical testing	Citation Link,
SCV003338359	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 5, 2022)	germline	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

SCV000862164

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL ClinVar v180209 classification definitions)

Uncertain significance
(Jun 26, 2018)

germline

clinical testing

Citation Link,

SCV003338359

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 5, 2022)

germline

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	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Eurofins Ntd Llc (ga), SCV000862164.1

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

#	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		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003338359.2

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCB11 protein function. ClinVar contains an entry for this variant (Variation ID: 597818). This variant has not been reported in the literature in individuals affected with ABCB11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 846 of the ABCB11 protein (p.Trp846Cys).

#	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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