NM_183377.2:c.859+10805C>T

Variant names:

• chr17-33101112-G-A
• rs8070997
• NM_183377.2:c.859+10805C>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.859+10805C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,144 control chromosomes in the GnomAD database, including 60,849 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 0.89 (60849 hom., cov: 31)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 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.859+10805C>T		intron	N/A	NP_899233.1
	ASIC2	NM_001094.5		c.706+10805C>T		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.859+10805C>T		intron	N/A	ENSP00000225823.2
	ASIC2	ENST00000359872.6	TSL:1	c.706+10805C>T		intron	N/A	ENSP00000352934.6
	ASIC2	ENST00000448983.1	TSL:3	n.264+10805C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135955 AN: 152026 Hom.: 60813 Cov.: 31

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.894 AC: 136047 AN: 152144 Hom.: 60849 Cov.: 31 AF XY: 0.893 AC XY: 66388 AN XY: 74362

African (AFR) AF: 0.921 AC: 38234 AN: 41518

American (AMR) AF: 0.898 AC: 13725 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3249 AN: 3472

East Asian (EAS) AF: 0.872 AC: 4488 AN: 5144

South Asian (SAS) AF: 0.908 AC: 4375 AN: 4816

European-Finnish (FIN) AF: 0.855 AC: 9054 AN: 10588

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59873 AN: 68004

Other (OTH) AF: 0.900 AC: 1900 AN: 2112

Alfa AF: 0.887 Hom.: 142942

Bravo AF: 0.898

Asia WGS AF: 0.908 AC: 3160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.41
DANN	Benign	0.62
PhyloP100		-1.4
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: rs8070997; hg19: chr17-31428130;