NM_019594.4(LRRC8A):c.275C>T (p.Thr92Met) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 4, 2023
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:: RCV001941495.7

Allele description [Variation Report for NM_019594.4(LRRC8A):c.275C>T (p.Thr92Met)]

NM_019594.4(LRRC8A):c.275C>T (p.Thr92Met)

Gene:

LRRC8A:leucine rich repeat containing 8 VRAC subunit A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_019594.4(LRRC8A):c.275C>T (p.Thr92Met)

HGVS:

NC_000009.12:g.128907439C>T
NG_009630.1:g.30328C>T
NM_001127244.2:c.275C>T
NM_001127245.2:c.275C>T
NM_019594.4:c.275C>TMANE SELECT
NP_001120716.1:p.Thr92Met
NP_001120717.1:p.Thr92Met
NP_062540.2:p.Thr92Met
LRG_80:g.30328C>T
NC_000009.11:g.131669718C>T

Protein change:

T92M

Links:

dbSNP: rs150865438

NCBI 1000 Genomes Browser:

rs150865438

Molecular consequence:

NM_001127244.2:c.275C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127245.2:c.275C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_019594.4:c.275C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Caenorhabditis elegans CUB_2 domain-containing protein (Y41D4B.17), mRNA
Caenorhabditis elegans CUB_2 domain-containing protein (Y41D4B.17), mRNA
gi|1734328210|ref|NM_067698.5|

Nucleotide
LYMARV-amide [Caenorhabditis elegans]
LYMARV-amide [Caenorhabditis elegans]
gi|1845979826|ref|NP_001370577.1|

Protein
Caenorhabditis elegans Double-Strand Break factor (dsb-2), mRNA
Caenorhabditis elegans Double-Strand Break factor (dsb-2), mRNA
gi|1972257037|ref|NM_001383993.2|

Nucleotide
recombination activating protein 1, partial [Xiphophorus alvarezi]
recombination activating protein 1, partial [Xiphophorus alvarezi]
gi|632799016|gb|AHZ35063.1|

Protein
Major facilitator superfamily (MFS) profile domain-containing protein [Caenorhab...
Major facilitator superfamily (MFS) profile domain-containing protein [Caenorhabditis elegans]
gi|17550316|ref|NP_510705.1|

Protein

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
SCV002223740	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 4, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27577878, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002223740

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 4, 2023)

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

Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders.

Stray-Pedersen A, Sorte HS, Samarakoon P, Gambin T, Chinn IK, Coban Akdemir ZH, Erichsen HC, Forbes LR, Gu S, Yuan B, Jhangiani SN, Muzny DM, Rødningen OK, Sheng Y, Nicholas SK, Noroski LM, Seeborg FO, Davis CM, Canter DL, Mace EM, Vece TJ, Allen CE, et al.

J Allergy Clin Immunol. 2017 Jan;139(1):232-245. doi: 10.1016/j.jaci.2016.05.042. Epub 2016 Jul 16. Erratum in: J Allergy Clin Immunol. 2018 Feb;141(2):832. doi: 10.1016/j.jaci.2017.12.975.

PubMed [citation]

PMID:: 27577878
PMCID:: PMC5222743

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, SCV002223740.3

#	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 threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 92 of the LRRC8A protein (p.Thr92Met). This variant is present in population databases (rs150865438, gnomAD 0.02%). This missense change has been observed in individual(s) with primary immunodeficiency disease (PMID: 27577878). ClinVar contains an entry for this variant (Variation ID: 1442334). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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

ClinVar

Relating variation to medicine