17-34050679-A-C

Variant names:

• chr17-34050679-A-C
• rs1978136
• ENST00000359872.6:c.555+105299T>G

Variant summary

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

The ENST00000359872.6(ASIC2):​c.555+105299T>G 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 152,108 control chromosomes in the GnomAD database, including 10,027 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 (10027 hom., cov: 33)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 3 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]

LOC107987247 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359872.6. 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_001094.5		c.555+105299T>G		intron	N/A	NP_001085.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000359872.6	TSL:1	c.555+105299T>G		intron	N/A	ENSP00000352934.6
	ENSG00000265356	ENST00000636421.1	TSL:5	n.274+1025T>G		intron	N/A
	ENSG00000279668	ENST00000636506.1	TSL:5	n.746+20138T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51897 AN: 151990 Hom.: 9999 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.342 AC: 51974 AN: 152108 Hom.: 10027 Cov.: 33 AF XY: 0.344 AC XY: 25589 AN XY: 74356

African (AFR) AF: 0.526 AC: 21830 AN: 41490

American (AMR) AF: 0.294 AC: 4485 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1070 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2151 AN: 5172

South Asian (SAS) AF: 0.184 AC: 888 AN: 4820

European-Finnish (FIN) AF: 0.318 AC: 3354 AN: 10554

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17197 AN: 68008

Other (OTH) AF: 0.319 AC: 674 AN: 2112

Alfa AF: 0.282 Hom.: 24785

Bravo AF: 0.351

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.77
PhyloP100		-0.017
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: rs1978136; hg19: chr17-32377698;