X-14690691-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002063.4(GLRA2):c.931-19G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00494 in 923,786 control chromosomes in the GnomAD database, including 97 homozygotes. There are 706 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (68 hom., 516 hem., cov: 22)
  • Exomes 𝑓: 0.0026 (29 hom. 190 hem.)
• Consequence: GLRA2 NM_002063.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.93

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-14690691-G-C is Benign according to our data. Variant chrX-14690691-G-C is described in ClinVar as [Benign]. Clinvar id is 1339589.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRA2	NM_002063.4	c.931-19G>C		intron_variant		ENST00000218075.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRA2	ENST00000218075.9	c.931-19G>C		intron_variant		1	NM_002063.4	A1

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 2476 AN: 109121 Hom.: 68 Cov.: 22 AF XY: 0.0161 AC XY: 512 AN XY: 31859

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00823

Gnomad ASJ AF: 0.00192

Gnomad EAS AF: 0.000285

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00427

Gnomad NFE AF: 0.000610

Gnomad OTH AF: 0.0207

GnomAD3 exomes AF: 0.00859 AC: 1068 AN: 124260 Hom.: 13 AF XY: 0.00193 AC XY: 75 AN XY: 38956

Gnomad AFR exome AF: 0.0850

Gnomad AMR exome AF: 0.00604

Gnomad ASJ exome AF: 0.00155

Gnomad EAS exome AF: 0.000102

Gnomad SAS exome AF: 0.000362

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000480

Gnomad OTH exome AF: 0.00513

GnomAD4 exome AF: 0.00256 AC: 2082 AN: 814624 Hom.: 29 Cov.: 17 AF XY: 0.000800 AC XY: 190 AN XY: 237400

Gnomad4 AFR exome AF: 0.0730

Gnomad4 AMR exome AF: 0.00516

Gnomad4 ASJ exome AF: 0.00135

Gnomad4 EAS exome AF: 0.0000774

Gnomad4 SAS exome AF: 0.000346

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000340

Gnomad4 OTH exome AF: 0.00541

GnomAD4 genome AF: 0.0227 AC: 2480 AN: 109162 Hom.: 68 Cov.: 22 AF XY: 0.0162 AC XY: 516 AN XY: 31912

Gnomad4 AFR AF: 0.0779

Gnomad4 AMR AF: 0.00822

Gnomad4 ASJ AF: 0.00192

Gnomad4 EAS AF: 0.000286

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000611

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0147 Hom.: 74

Bravo AF: 0.0292

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 03, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.63
Dann	Benign	0.31

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

Other links and lift over

dbSNP: rs112316577; hg19: chrX-14708813; COSMIC: COSV54349398;