rs6630716

Variant names:

• chrX-14616743-C-T
• rs6630716
• NM_002063.4:c.930+7538C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002063.4(GLRA2):​c.930+7538C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 111,151 control chromosomes in the GnomAD database, including 2,487 homozygotes. There are 7,925 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 0.24 (2487 hom., 7925 hem., cov: 23)
• Consequence: GLRA2 NM_002063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, X-linked, syndromic, Pilorge type

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA2	NM_002063.4	c.930+7538C>T		intron_variant	Intron 7 of 8	ENST00000218075.9	NP_002054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA2	ENST00000218075.9	c.930+7538C>T		intron_variant	Intron 7 of 8	1	NM_002063.4	ENSP00000218075.4
GLRA2	ENST00000355020.9	c.930+7538C>T		intron_variant	Intron 7 of 8	1		ENSP00000347123.4
GLRA2	ENST00000415367.2	n.1181+7538C>T		intron_variant	Intron 7 of 8	3
GLRA2	ENST00000443437.6	n.*857+7538C>T		intron_variant	Intron 9 of 10	2		ENSP00000387756.3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 26939 AN: 111098 Hom.: 2487 Cov.: 23

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0113

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.233

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.242 AC: 26948 AN: 111151 Hom.: 2487 Cov.: 23 AF XY: 0.237 AC XY: 7925 AN XY: 33489

African (AFR) AF: 0.178 AC: 5465 AN: 30743

American (AMR) AF: 0.192 AC: 2014 AN: 10468

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 564 AN: 2623

East Asian (EAS) AF: 0.0113 AC: 40 AN: 3529

South Asian (SAS) AF: 0.240 AC: 641 AN: 2675

European-Finnish (FIN) AF: 0.304 AC: 1797 AN: 5913

Middle Eastern (MID) AF: 0.228 AC: 49 AN: 215

European-Non Finnish (NFE) AF: 0.300 AC: 15832 AN: 52808

Other (OTH) AF: 0.223 AC: 336 AN: 1507

Alfa AF: 0.269 Hom.: 4979

Bravo AF: 0.229

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.5
DANN	Benign	0.53
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6630716; hg19: chrX-14634865; COSMIC: COSV99491098;