17-33292727-G-C

Variant names:

• chr17-33292727-G-C
• rs7214382
• NM_183377.2:c.-612C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183377.2(ASIC2):​c.-612C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 985,678 control chromosomes in the GnomAD database, including 109,958 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 0.50 (19391 hom., cov: 33)
  • Exomes 𝑓: 0.47 (90567 hom.)
• Consequence: ASIC2 NM_183377.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183377.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_183377.2	MANE Select	c.-612C>G		5_prime_UTR	Exon 1 of 10	NP_899233.1
	ASIC2	NM_001094.5		c.556-180660C>G		intron	N/A	NP_001085.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000225823.7	TSL:1 MANE Select	c.-612C>G		5_prime_UTR	Exon 1 of 10	ENSP00000225823.2
	ASIC2	ENST00000359872.6	TSL:1	c.556-180660C>G		intron	N/A	ENSP00000352934.6

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76330 AN: 151906 Hom.: 19360 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.465 AC: 387908 AN: 833656 Hom.: 90567 Cov.: 31 AF XY: 0.466 AC XY: 179276 AN XY: 385114

African (AFR) AF: 0.549 AC: 8666 AN: 15794

American (AMR) AF: 0.521 AC: 513 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 2740 AN: 5154

East Asian (EAS) AF: 0.751 AC: 2741 AN: 3652

South Asian (SAS) AF: 0.417 AC: 6868 AN: 16466

European-Finnish (FIN) AF: 0.457 AC: 128 AN: 280

Middle Eastern (MID) AF: 0.529 AC: 858 AN: 1622

European-Non Finnish (NFE) AF: 0.462 AC: 351962 AN: 762374

Other (OTH) AF: 0.491 AC: 13432 AN: 27330

GnomAD4 genome AF: 0.503 AC: 76410 AN: 152022 Hom.: 19391 Cov.: 33 AF XY: 0.503 AC XY: 37351 AN XY: 74310

African (AFR) AF: 0.531 AC: 22024 AN: 41506

American (AMR) AF: 0.501 AC: 7668 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1822 AN: 3462

East Asian (EAS) AF: 0.741 AC: 3783 AN: 5108

South Asian (SAS) AF: 0.420 AC: 2027 AN: 4824

European-Finnish (FIN) AF: 0.485 AC: 5133 AN: 10594

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.476 AC: 32328 AN: 67922

Other (OTH) AF: 0.513 AC: 1083 AN: 2112

Alfa AF: 0.348 Hom.: 941

Bravo AF: 0.512

Asia WGS AF: 0.577 AC: 2006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		-2.0
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7214382; hg19: chr17-31619745;