NM_183377.2:c.1350-563C>T

Variant names:

• chr17-33021873-G-A
• rs16571
• NM_183377.2:c.1350-563C>T

Variant summary

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

The NM_183377.2(ASIC2):​c.1350-563C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,150 control chromosomes in the GnomAD database, including 6,913 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 0.29 (6913 hom., cov: 33)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_183377.2	MANE Select	c.1350-563C>T		intron	N/A	NP_899233.1	Q16515-2
	ASIC2	NM_001094.5		c.1197-563C>T		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.1350-563C>T		intron	N/A	ENSP00000225823.2	Q16515-2
	ASIC2	ENST00000359872.6	TSL:1	c.1197-563C>T		intron	N/A	ENSP00000352934.6	Q16515-1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44262 AN: 152032 Hom.: 6907 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.291 AC: 44265 AN: 152150 Hom.: 6913 Cov.: 33 AF XY: 0.285 AC XY: 21220 AN XY: 74368

African (AFR) AF: 0.213 AC: 8845 AN: 41508

American (AMR) AF: 0.238 AC: 3648 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3470

East Asian (EAS) AF: 0.100 AC: 518 AN: 5178

South Asian (SAS) AF: 0.233 AC: 1123 AN: 4826

European-Finnish (FIN) AF: 0.366 AC: 3877 AN: 10584

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23987 AN: 67968

Other (OTH) AF: 0.285 AC: 603 AN: 2116

Alfa AF: 0.297 Hom.: 1033

Bravo AF: 0.279

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.54
DANN	Benign	0.63
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16571; hg19: chr17-31348891;