rs5934186

Variant names:

• chrX-14660373-A-C
• rs5934186
• NM_002063.4:c.931-30337A>C

Variant summary

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

The NM_002063.4(GLRA2):​c.931-30337A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 110,793 control chromosomes in the GnomAD database, including 1,760 homozygotes. There are 6,459 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 0.20 (1760 hom., 6459 hem., cov: 22)
• Consequence: GLRA2 NM_002063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002063.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRA2	NM_002063.4	MANE Select	c.931-30337A>C		intron	N/A	NP_002054.1
	GLRA2	NM_001118885.2		c.931-30337A>C		intron	N/A	NP_001112357.1
	GLRA2	NM_001118886.2		c.931-30337A>C		intron	N/A	NP_001112358.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRA2	ENST00000218075.9	TSL:1 MANE Select	c.931-30337A>C		intron	N/A	ENSP00000218075.4
	GLRA2	ENST00000355020.9	TSL:1	c.931-30337A>C		intron	N/A	ENSP00000347123.4
	GLRA2	ENST00000415367.2	TSL:3	n.1182-30337A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.201 AC: 22258 AN: 110739 Hom.: 1760 Cov.: 22

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.201 AC: 22253 AN: 110793 Hom.: 1760 Cov.: 22 AF XY: 0.195 AC XY: 6459 AN XY: 33097

African (AFR) AF: 0.142 AC: 4331 AN: 30510

American (AMR) AF: 0.154 AC: 1606 AN: 10451

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 615 AN: 2642

East Asian (EAS) AF: 0.0788 AC: 276 AN: 3504

South Asian (SAS) AF: 0.169 AC: 438 AN: 2597

European-Finnish (FIN) AF: 0.246 AC: 1438 AN: 5839

Middle Eastern (MID) AF: 0.219 AC: 47 AN: 215

European-Non Finnish (NFE) AF: 0.243 AC: 12847 AN: 52840

Other (OTH) AF: 0.193 AC: 295 AN: 1527

Alfa AF: 0.221 Hom.: 17123

Bravo AF: 0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.51
PhyloP100		-0.28
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: rs5934186; hg19: chrX-14678495;