chrX-14581236-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_002063.4(GLRA2):​c.324G>A​(p.Ala108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,187,078 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000020 ( 0 hom. 9 hem. )

Consequence

GLRA2
NM_002063.4 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0720
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant X-14581236-G-A is Benign according to our data. Variant chrX-14581236-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3039889.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.072 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 9 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GLRA2NM_002063.4 linkuse as main transcriptc.324G>A p.Ala108= synonymous_variant 4/9 ENST00000218075.9 NP_002054.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GLRA2ENST00000218075.9 linkuse as main transcriptc.324G>A p.Ala108= synonymous_variant 4/91 NM_002063.4 ENSP00000218075 A1P23416-1
GLRA2ENST00000355020.9 linkuse as main transcriptc.324G>A p.Ala108= synonymous_variant 4/91 ENSP00000347123 P4P23416-2
GLRA2ENST00000415367.2 linkuse as main transcriptn.575G>A non_coding_transcript_exon_variant 4/93
GLRA2ENST00000443437.6 linkuse as main transcriptc.*251G>A 3_prime_UTR_variant, NMD_transcript_variant 6/112 ENSP00000387756 P23416-3

Frequencies

GnomAD3 genomes
AF:
0.0000269
AC:
3
AN:
111518
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33692
show subpopulations
Gnomad AFR
AF:
0.0000980
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
GnomAD3 exomes
AF:
0.0000437
AC:
8
AN:
183178
Hom.:
0
AF XY:
0.0000295
AC XY:
2
AN XY:
67694
show subpopulations
Gnomad AFR exome
AF:
0.000152
Gnomad AMR exome
AF:
0.000109
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000144
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
22
AN:
1075505
Hom.:
0
Cov.:
27
AF XY:
0.0000263
AC XY:
9
AN XY:
342651
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000853
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000996
Gnomad4 SAS exome
AF:
0.0000746
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.0000122
Gnomad4 OTH exome
AF:
0.0000221
GnomAD4 genome
AF:
0.0000269
AC:
3
AN:
111573
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33757
show subpopulations
Gnomad4 AFR
AF:
0.0000978
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:
0.0000793

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

GLRA2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesSep 10, 2019This 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
-0.47
CADD
Benign
6.4
DANN
Benign
0.70

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.

Other links and lift over

dbSNP: rs199797447; hg19: chrX-14599358; COSMIC: COSV54338643; API