chrX-14608992-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7

The NM_002063.4(GLRA2):ā€‹c.717A>Gā€‹(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 š‘“: 0.0000078 ( 0 hom. 1 hem. )
Failed GnomAD Quality Control

Consequence

GLRA2
NM_002063.4 splice_region, synonymous

Scores

2
Splicing: ADA: 0.0001511
2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.116
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 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
GLRA2NM_002063.4 linkuse as main transcriptc.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
GLRA2ENST00000218075.9 linkuse as main transcriptc.717A>G p.Gly239= splice_region_variant, synonymous_variant 7/91 NM_002063.4 ENSP00000218075 A1P23416-1
GLRA2ENST00000355020.9 linkuse as main transcriptc.717A>G p.Gly239= splice_region_variant, synonymous_variant 7/91 ENSP00000347123 P4P23416-2
GLRA2ENST00000415367.2 linkuse as main transcriptn.968A>G splice_region_variant, non_coding_transcript_exon_variant 7/93
GLRA2ENST00000443437.6 linkuse as main transcriptc.*644A>G splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant 9/112 ENSP00000387756 P23416-3

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
show subpopulations
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
LINK: link

Submissions by phenotype

GLRA2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 23, 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
-0.42
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

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

Other links and lift over

dbSNP: rs2090369987; hg19: chrX-14627114; API