rs10521643

Positions:

• chrX-14702539-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002063.4(GLRA2):​c.1080+11680T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 111,916 control chromosomes in the GnomAD database, including 524 homozygotes. There are 2,544 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.081 (524 hom., 2544 hem., cov: 23)
• Consequence: GLRA2 NM_002063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

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 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRA2	NM_002063.4	c.1080+11680T>G		intron_variant		ENST00000218075.9	NP_002054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRA2	ENST00000218075.9	c.1080+11680T>G		intron_variant		1	NM_002063.4	ENSP00000218075.4

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 9108 AN: 111864 Hom.: 527 Cov.: 23 AF XY: 0.0746 AC XY: 2540 AN XY: 34030

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0389

Gnomad FIN AF: 0.00737

Gnomad MID AF: 0.0295

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0703

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0814 AC: 9108 AN: 111916 Hom.: 524 Cov.: 23 AF XY: 0.0746 AC XY: 2544 AN XY: 34092

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.0211

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0393

Gnomad4 FIN AF: 0.00737

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.0694

Alfa AF: 0.0598 Hom.: 726

Bravo AF: 0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.37
DANN	Benign	0.88

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: rs10521643; hg19: chrX-14720661;