chrX-14730288-G-C

Position:

• chrX-14730288-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002063.4(GLRA2):​c.1162G>C​(p.Ala388Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: GLRA2 NM_002063.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.99

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]

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3015093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRA2	NM_002063.4	c.1162G>C	p.Ala388Pro	missense_variant	9/9	ENST00000218075.9	NP_002054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRA2	ENST00000218075.9	c.1162G>C	p.Ala388Pro	missense_variant	9/9	1	NM_002063.4	ENSP00000218075	A1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 21

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.1162G>C (p.A388P) alteration is located in exon 9 (coding exon 9) of the GLRA2 gene. This alteration results from a G to C substitution at nucleotide position 1162, causing the alanine (A) at amino acid position 388 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.0053	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;T;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.93	.;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.37	N;N;N
REVEL	Benign	0.27
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.92, 0.0010	.;P;B
Vest4		0.35
MutPred		0.60		.;Gain of disorder (P = 0.051);Gain of disorder (P = 0.051);
MVP		0.85
MPC		1.4
ClinPred		0.43	T
GERP RS		4.6
Varity_R		0.31
gMVP		0.74

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: rs2091976631; hg19: chrX-14748410;