rs28935

Variant names:

• chr17-33013426-A-G
• rs28935
• NM_183377.2:c.*539T>C

Variant summary

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

The NM_183377.2(ASIC2):​c.*539T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 154,990 control chromosomes in the GnomAD database, including 4,983 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 0.23 (4940 hom., cov: 33)
  • Exomes 𝑓: 0.16 (43 hom.)
• Consequence: ASIC2 NM_183377.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 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.*539T>C		3_prime_UTR	Exon 10 of 10	NP_899233.1
	ASIC2	NM_001094.5		c.*539T>C		3_prime_UTR	Exon 10 of 10	NP_001085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000225823.7	TSL:1 MANE Select	c.*539T>C		3_prime_UTR	Exon 10 of 10	ENSP00000225823.2
	ASIC2	ENST00000359872.6	TSL:1	c.*539T>C		3_prime_UTR	Exon 10 of 10	ENSP00000352934.6

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35016 AN: 152032 Hom.: 4919 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.158 AC: 449 AN: 2840 Hom.: 43 Cov.: 0 AF XY: 0.151 AC XY: 227 AN XY: 1500

African (AFR) AF: 0.300 AC: 6 AN: 20

American (AMR) AF: 0.126 AC: 96 AN: 762

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 2 AN: 10

East Asian (EAS) AF: 0.271 AC: 57 AN: 210

South Asian (SAS) AF: 0.262 AC: 43 AN: 164

European-Finnish (FIN) AF: 0.111 AC: 18 AN: 162

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.152 AC: 215 AN: 1416

Other (OTH) AF: 0.125 AC: 12 AN: 96

GnomAD4 genome AF: 0.231 AC: 35089 AN: 152150 Hom.: 4940 Cov.: 33 AF XY: 0.232 AC XY: 17279 AN XY: 74370

African (AFR) AF: 0.379 AC: 15728 AN: 41498

American (AMR) AF: 0.160 AC: 2454 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3468

East Asian (EAS) AF: 0.422 AC: 2176 AN: 5162

South Asian (SAS) AF: 0.278 AC: 1342 AN: 4826

European-Finnish (FIN) AF: 0.133 AC: 1409 AN: 10606

Middle Eastern (MID) AF: 0.276 AC: 80 AN: 290

European-Non Finnish (NFE) AF: 0.155 AC: 10551 AN: 67974

Other (OTH) AF: 0.229 AC: 485 AN: 2114

Alfa AF: 0.185 Hom.: 1285

Bravo AF: 0.235

Asia WGS AF: 0.391 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.71
DANN	Benign	0.45
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: rs28935; hg19: chr17-31340444;