Variant X-14690691-GTC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP6_ModerateBS2_Supporting

The NM_002063.4(GLRA2):c.931-4_931-3del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00868 in 833,596 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.010 ( 0 hom. 2 hem. )

Consequence

GLRA2
NM_002063.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.180

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP6

Variant X-14690691-GTC-G is Benign according to our data. Variant chrX-14690691-GTC-G is described in ClinVar as [Benign]. Clinvar id is 2232252.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRA2	NM_002063.4 linkuse as main transcript	c.931-4_931-3del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000218075.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRA2	ENST00000218075.9 linkuse as main transcript	c.931-4_931-3del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002063.4	A1	P23416-1

Frequencies

GnomAD3 genomes

AF:

0.0000917

AC:

AN:

109014

Hom.:

Cov.:

AF XY:

0.0000629

AC XY:

AN XY:

31804

show subpopulations

Gnomad AFR

AF:

0.0000671

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000588

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000191

Gnomad OTH

AF:

0.000692

GnomAD3 exomes

AF:

0.00321

AC:

399

AN:

124260

Hom.:

AF XY:

0.0000770

AC XY:

AN XY:

38956

show subpopulations

Gnomad AFR exome

AF:

0.000657

Gnomad AMR exome

AF:

0.00438

Gnomad ASJ exome

AF:

0.00642

Gnomad EAS exome

AF:

0.00215

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.00416

Gnomad NFE exome

AF:

0.00320

Gnomad OTH exome

AF:

0.00410

GnomAD4 exome

AF:

0.00997

AC:

7223

AN:

724539

Hom.:

AF XY:

0.00000983

AC XY:

AN XY:

203377

show subpopulations

Gnomad4 AFR exome

AF:

0.00432

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.00692

Gnomad4 EAS exome

AF:

0.00268

Gnomad4 SAS exome

AF:

0.00510

Gnomad4 FIN exome

AF:

0.00365

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.00796

GnomAD4 genome

AF:

0.000101

AC:

AN:

109057

Hom.:

Cov.:

AF XY:

0.0000628

AC XY:

AN XY:

31857

show subpopulations

Gnomad4 AFR

AF:

0.000100

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000191

Gnomad4 OTH

AF:

0.000683

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 17, 2022

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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