chrX-14607193-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002063.4(GLRA2):​c.640G>C​(p.Glu214Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

GLRA2
NM_002063.4 missense

Scores

2
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.90
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GLRA2NM_002063.4 linkuse as main transcriptc.640G>C p.Glu214Gln missense_variant 6/9 ENST00000218075.9 NP_002054.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GLRA2ENST00000218075.9 linkuse as main transcriptc.640G>C p.Glu214Gln missense_variant 6/91 NM_002063.4 ENSP00000218075 A1P23416-1
GLRA2ENST00000355020.9 linkuse as main transcriptc.640G>C p.Glu214Gln missense_variant 6/91 ENSP00000347123 P4P23416-2
GLRA2ENST00000415367.2 linkuse as main transcriptn.891G>C non_coding_transcript_exon_variant 6/93
GLRA2ENST00000443437.6 linkuse as main transcriptc.*567G>C 3_prime_UTR_variant, NMD_transcript_variant 8/112 ENSP00000387756 P23416-3

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
25
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual developmental disorder, X-linked, syndromic, Pilorge type Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingFoundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human GeneticsOct 18, 2024A heterozygous missense variant in exon 6 of the GLRA2 gene that results in the amino acid substitution of Glutamine for Glutamic acid at codon 214 (p.Glu214Gln) was detected. This variant has not been reported in the 1000 genomes, gnomAD (v3.1), gnomAD (v2.1), and topmed databases. The in silico predictions of the variant are damaging by SIFT and LRT. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.022
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.47
.;T;.;.
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D;D;D
M_CAP
Pathogenic
0.53
D
MetaRNN
Uncertain
0.57
D;D;D;D
MetaSVM
Uncertain
0.0043
D
MutationAssessor
Benign
1.7
.;L;L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.3
N;N;N;N
REVEL
Uncertain
0.49
Sift
Benign
0.095
T;D;D;D
Sift4G
Benign
0.16
T;T;T;T
Polyphen
0.099, 0.012
.;B;B;.
Vest4
0.27
MutPred
0.52
.;Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);.;
MVP
0.92
MPC
2.1
ClinPred
0.80
D
GERP RS
5.6
Varity_R
0.51
gMVP
0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-14625315; API