rs367596005

Variant names:

• chr17-33014047-G-A
• rs367596005
• NM_183377.2:c.1610C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-33014047-G-A
• chr17-33014047-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_183377.2(ASIC2):​c.1610C>T​(p.Pro537Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASIC2 NM_183377.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.18

Genes affected

ASIC2 (HGNC:99): (acid sensing ion channel subunit 2) This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene may play a role in neurotransmission. In addition, a heteromeric association between this member and acid-sensing (proton-gated) ion channel 3 has been observed to co-assemble into proton-gated channels sensitive to gadolinium. Alternative splicing has been observed at this locus and two variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.117622554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2	c.1610C>T	p.Pro537Leu	missense_variant	Exon 10 of 10	ENST00000225823.7	NP_899233.1
ASIC2	NM_001094.5	c.1457C>T	p.Pro486Leu	missense_variant	Exon 10 of 10		NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000225823.7	c.1610C>T	p.Pro537Leu	missense_variant	Exon 10 of 10	1	NM_183377.2	ENSP00000225823.2
ASIC2	ENST00000359872.6	c.1457C>T	p.Pro486Leu	missense_variant	Exon 10 of 10	1		ENSP00000352934.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.14	.;T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	.;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.038
Sift	Benign	0.32	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.13	.;B
Vest4		0.35
MutPred		0.29		.;Loss of sheet (P = 0.0104);
MVP		0.13
MPC		0.56
ClinPred		0.46	T
GERP RS		5.0
Varity_R		0.13
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs367596005; hg19: chr17-31341065;