NM_183377.2:c.709-2102A>G

Variant names:

• chr17-33114169-T-C
• rs16968024
• NM_183377.2:c.709-2102A>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.709-2102A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,258 control chromosomes in the GnomAD database, including 2,361 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 0.17 (2361 hom., cov: 33)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 5 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]

ENSG00000266535 (HGNC:58564):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 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.709-2102A>G		intron	N/A	NP_899233.1
	ASIC2	NM_001094.5		c.556-2102A>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.709-2102A>G		intron	N/A	ENSP00000225823.2
	ASIC2	ENST00000359872.6	TSL:1	c.556-2102A>G		intron	N/A	ENSP00000352934.6
	ASIC2	ENST00000448983.1	TSL:3	n.114-2102A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25662 AN: 152140 Hom.: 2360 Cov.: 33

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0999

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.169 AC: 25684 AN: 152258 Hom.: 2361 Cov.: 33 AF XY: 0.168 AC XY: 12487 AN XY: 74452

African (AFR) AF: 0.121 AC: 5009 AN: 41550

American (AMR) AF: 0.112 AC: 1715 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3470

East Asian (EAS) AF: 0.100 AC: 521 AN: 5192

South Asian (SAS) AF: 0.153 AC: 738 AN: 4822

European-Finnish (FIN) AF: 0.239 AC: 2533 AN: 10596

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14146 AN: 68016

Other (OTH) AF: 0.161 AC: 340 AN: 2108

Alfa AF: 0.184 Hom.: 5124

Bravo AF: 0.154

Asia WGS AF: 0.109 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.72
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: rs16968024; hg19: chr17-31441187;