Variant X-14730215-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002063.4(GLRA2):c.1089C>T(p.Asp363=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,197,288 control chromosomes in the GnomAD database, including 74 homozygotes. There are 1,003 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 40 hom., 509 hem., cov: 22)

Exomes 𝑓: 0.0019 ( 34 hom. 494 hem. )

Consequence

GLRA2
NM_002063.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.585

Variant links:

Genes affected

GLRA2 (HGNC:4327): (glycine receptor alpha 2) The glycine receptor consists of two subunits, alpha and beta, and acts as a pentamer. The protein encoded by this gene is an alpha subunit and can bind strychnine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

GLRA2 links:

FANCB (HGNC:3583): (FA complementation group B) This gene encodes a member of the Fanconi anemia complementation group B. This protein is assembled into a nucleoprotein complex that is involved in the repair of DNA lesions. Mutations in this gene can cause chromosome instability and VACTERL syndrome with hydrocephalus. [provided by RefSeq, Apr 2016]

FANCB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant X-14730215-C-T is Benign according to our data. Variant chrX-14730215-C-T is described in ClinVar as [Benign]. Clinvar id is 780683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.585 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRA2	NM_002063.4 linkuse as main transcript	c.1089C>T	p.Asp363=	synonymous_variant	9/9	ENST00000218075.9	NP_002054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRA2	ENST00000218075.9 linkuse as main transcript	c.1089C>T	p.Asp363=	synonymous_variant	9/9	1	NM_002063.4	ENSP00000218075	A1	P23416-1

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

1999

AN:

111172

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

509

AN XY:

33384

show subpopulations

Gnomad AFR

AF:

0.0605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00847

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.00530

AC:

966

AN:

182206

Hom.:

AF XY:

0.00341

AC XY:

228

AN XY:

66880

show subpopulations

Gnomad AFR exome

AF:

0.0634

Gnomad AMR exome

AF:

0.00369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000528

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000136

Gnomad OTH exome

AF:

0.00400

GnomAD4 exome

AF:

0.00186

AC:

2018

AN:

1086065

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

494

AN XY:

352643

show subpopulations

Gnomad4 AFR exome

AF:

0.0580

Gnomad4 AMR exome

AF:

0.00498

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.0000558

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.00468

GnomAD4 genome

AF:

0.0180

AC:

1999

AN:

111223

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

509

AN XY:

33445

show subpopulations

Gnomad4 AFR

AF:

0.0604

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000188

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0216

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000595

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

GLRA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.97

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over