X-14581411-G-T

Variant names:

• chrX-14581411-G-T
• rs775951787
• NM_002063.4:c.494+5G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002063.4(GLRA2):​c.494+5G>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000651 in 922,040 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000065 (0 hom. 4 hem.)
• Consequence: GLRA2 NM_002063.4 splice_region, intron
• Scores: Splicing: ADA: 0.9061
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BS2: High Hemizygotes in GnomAdExome4 at 4 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRA2	NM_002063.4	MANE Select	c.494+5G>T		splice_region intron	N/A	NP_002054.1	P23416-1
	GLRA2	NM_001118885.2		c.494+5G>T		splice_region intron	N/A	NP_001112357.1	P23416-1
	GLRA2	NM_001118886.2		c.494+5G>T		splice_region intron	N/A	NP_001112358.1	P23416-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRA2	ENST00000218075.9	TSL:1 MANE Select	c.494+5G>T		splice_region intron	N/A	ENSP00000218075.4	P23416-1
	GLRA2	ENST00000355020.9	TSL:1	c.494+5G>T		splice_region intron	N/A	ENSP00000347123.4	P23416-2
	GLRA2	ENST00000415367.2	TSL:3	n.745+5G>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 181216 AF XY: 0.0000302

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000248

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000651 AC: 6 AN: 922040 Hom.: 0 Cov.: 19 AF XY: 0.0000163 AC XY: 4 AN XY: 246072

African (AFR) AF: 0.00 AC: 0 AN: 23116

American (AMR) AF: 0.00 AC: 0 AN: 34989

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18183

East Asian (EAS) AF: 0.00 AC: 0 AN: 29413

South Asian (SAS) AF: 0.00 AC: 0 AN: 50298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3743

European-Non Finnish (NFE) AF: 0.00000880 AC: 6 AN: 681538

Other (OTH) AF: 0.00 AC: 0 AN: 40368

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.90
PhyloP100		4.2
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.91
dbscSNV1_RF	Benign	0.59
SpliceAI score (max)		0.010		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: rs775951787; hg19: chrX-14599533;