X-14608992-A-G

Position:

• chrX-14608992-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_002063.4(GLRA2):​c.717A>G​(p.Gly239=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000078 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: GLRA2 NM_002063.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001511
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.116

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant X-14608992-A-G is Benign according to our data. Variant chrX-14608992-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3350603.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.116 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRA2	NM_002063.4	c.717A>G	p.Gly239=	splice_region_variant, synonymous_variant	7/9	ENST00000218075.9	NP_002054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRA2	ENST00000218075.9	c.717A>G	p.Gly239=	splice_region_variant, synonymous_variant	7/9	1	NM_002063.4	ENSP00000218075	A1
GLRA2	ENST00000355020.9	c.717A>G	p.Gly239=	splice_region_variant, synonymous_variant	7/9	1		ENSP00000347123	P4
GLRA2	ENST00000415367.2	n.968A>G		splice_region_variant, non_coding_transcript_exon_variant	7/9	3
GLRA2	ENST00000443437.6	c.*644A>G		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	9/11	2		ENSP00000387756

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000776 AC: 7 AN: 901752 Hom.: 0 Cov.: 15 AF XY: 0.00000385 AC XY: 1 AN XY: 260048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000253

GnomAD4 genome Cov.: 21

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GLRA2-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 23, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.9
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.026
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: rs2090369987; hg19: chrX-14627114;