Variant X-14532285-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate

The NM_002063.4(GLRA2):c.115T>C(p.Ser39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,189,077 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000019 ( 0 hom. 1 hem. )

Consequence

GLRA2
NM_002063.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a topological_domain Extracellular (size 228) in uniprot entity GLRA2_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_002063.4

BP4

Computational evidence support a benign effect (MetaRNN=0.15941074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRA2	NM_002063.4 linkuse as main transcript	c.115T>C	p.Ser39Pro	missense_variant	2/9	ENST00000218075.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRA2	ENST00000218075.9 linkuse as main transcript	c.115T>C	p.Ser39Pro	missense_variant	2/9	1	NM_002063.4	A1	P23416-1
GLRA2	ENST00000355020.9 linkuse as main transcript	c.115T>C	p.Ser39Pro	missense_variant	2/9	1		P4	P23416-2
GLRA2	ENST00000415367.2 linkuse as main transcript	n.366T>C		non_coding_transcript_exon_variant	2/9	3
GLRA2	ENST00000443437.6 linkuse as main transcript	c.*82T>C		3_prime_UTR_variant, NMD_transcript_variant	4/11	2			P23416-3

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111770

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33990

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000186

AC:

AN:

1077307

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

344715

show subpopulations

Gnomad4 AFR exome

AF:

0.0000387

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:

0.00000121

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111770

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33990

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.115T>C (p.S39P) alteration is located in exon 2 (coding exon 2) of the GLRA2 gene. This alteration results from a T to C substitution at nucleotide position 115, causing the serine (S) at amino acid position 39 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

0.067

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.32

T;.;.

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.55

N;N;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.35

N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.91

P;B;.

Vest4

0.24

MutPred

0.23

Gain of catalytic residue at P38 (P = 0.0133);Gain of catalytic residue at P38 (P = 0.0133);.;

MVP

0.91

MPC

1.4

ClinPred

0.28

GERP RS

4.9

Varity_R

0.20

gMVP

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over