rs11650066

chr17-33960430-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359872.6(ASIC2):c.555+195548C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,090 control chromosomes in the GnomAD database, including 9,124 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9124 hom., cov: 32)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107985038	XR_001752840.2	n.222-23608C>T		intron_variant, non_coding_transcript_variant
ASIC2	NM_001094.5	c.555+195548C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000659958.1	n.130+23757C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51953 AN: 151970 Hom.: 9107 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.341

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.342 AC: 52016 AN: 152090 Hom.: 9124 Cov.: 32 AF XY: 0.339 AC XY: 25224 AN XY: 74336

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.341

Alfa AF: 0.347 Hom.: 21108

Bravo AF: 0.342

Asia WGS AF: 0.233 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.6
Dann	Benign	0.34

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

Other links and lift over

dbSNP: rs11650066; hg19: chr17-32287449;