17-33025914-C-T

Variant names:

• chr17-33025914-C-T
• rs16967902
• NM_183377.2:c.1195+12G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_183377.2(ASIC2):​c.1195+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,608,346 control chromosomes in the GnomAD database, including 96 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 0.0081 (5 hom., cov: 32)
  • Exomes 𝑓: 0.011 (91 hom.)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.787
• Publications: 4 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High AC in GnomAd4 at 1227 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_183377.2	MANE Select	c.1195+12G>A		intron	N/A	NP_899233.1
	ASIC2	NM_001094.5		c.1042+12G>A		intron	N/A	NP_001085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000225823.7	TSL:1 MANE Select	c.1195+12G>A		intron	N/A	ENSP00000225823.2
	ASIC2	ENST00000359872.6	TSL:1	c.1042+12G>A		intron	N/A	ENSP00000352934.6
	ASIC2	ENST00000448983.1	TSL:3	n.600+12G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00807 AC: 1227 AN: 152126 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00270

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00729 AC: 1788 AN: 245166 AF XY: 0.00740

Gnomad AFR exome AF: 0.00263

Gnomad AMR exome AF: 0.00745

Gnomad ASJ exome AF: 0.00421

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.00761

GnomAD4 exome AF: 0.0108 AC: 15734 AN: 1456102 Hom.: 91 Cov.: 30 AF XY: 0.0105 AC XY: 7571 AN XY: 724316

African (AFR) AF: 0.00205 AC: 68 AN: 33124

American (AMR) AF: 0.00817 AC: 357 AN: 43716

Ashkenazi Jewish (ASJ) AF: 0.00453 AC: 117 AN: 25840

East Asian (EAS) AF: 0.0000763 AC: 3 AN: 39314

South Asian (SAS) AF: 0.000504 AC: 43 AN: 85286

European-Finnish (FIN) AF: 0.00193 AC: 103 AN: 53334

Middle Eastern (MID) AF: 0.00261 AC: 15 AN: 5738

European-Non Finnish (NFE) AF: 0.0131 AC: 14484 AN: 1109620

Other (OTH) AF: 0.00905 AC: 544 AN: 60130

GnomAD4 genome AF: 0.00806 AC: 1227 AN: 152244 Hom.: 5 Cov.: 32 AF XY: 0.00793 AC XY: 590 AN XY: 74436

African (AFR) AF: 0.00270 AC: 112 AN: 41552

American (AMR) AF: 0.0141 AC: 215 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 834 AN: 68020

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.00481 Hom.: 1

Bravo AF: 0.00920

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.51
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16967902; hg19: chr17-31352932;