rs9892479

chr17-33094883-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_183377.2(ASIC2):c.860-5893C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 152,258 control chromosomes in the GnomAD database, including 129 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 0.040 (129 hom., cov: 33)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0398 (6067/152258) while in subpopulation NFE AF= 0.0474 (3225/68022). AF 95% confidence interval is 0.046. There are 129 homozygotes in gnomad4. There are 2886 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 6065 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC2	NM_183377.2	c.860-5893C>A		intron_variant		ENST00000225823.7
ASIC2	NM_001094.5	c.707-5893C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC2	ENST00000225823.7	c.860-5893C>A		intron_variant		1	NM_183377.2
ASIC2	ENST00000359872.6	c.707-5893C>A		intron_variant		1		P1
ASIC2	ENST00000448983.1	n.265-5893C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 6065 AN: 152140 Hom.: 129 Cov.: 33

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0264

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0398 AC: 6067 AN: 152258 Hom.: 129 Cov.: 33 AF XY: 0.0388 AC XY: 2886 AN XY: 74442

Gnomad4 AFR AF: 0.0405

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0266

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0474

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0415 Hom.: 28

Bravo AF: 0.0393

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.3
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs9892479; hg19: chr17-31421901;