Genetic Variant NM_183377.2:c.*539T>C (chr17-33013426-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.43

Publications

7 publications found

Variant links:

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]

ASIC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2 link	c.*539T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000225823.7	NP_899233.1	Q16515-2
ASIC2	NM_001094.5 link	c.*539T>C		3_prime_UTR_variant	Exon 10 of 10		NP_001085.2	Q16515-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000225823.7 link	c.*539T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_183377.2	ENSP00000225823.2		Q16515-2
ASIC2	ENST00000359872.6 link	c.*539T>C		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000352934.6		Q16515-1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

35016

AN:

152032

Hom.:

4919

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.151

AC XY:

227

AN XY:

1500

show subpopulations

African (AFR)

AF:

0.300

AC:

AN:

American (AMR)

AF:

0.126

AC:

AN:

762

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

AN:

East Asian (EAS)

AF:

0.271

AC:

AN:

210

South Asian (SAS)

AF:

0.262

AC:

AN:

164

European-Finnish (FIN)

AF:

0.111

AC:

AN:

162

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.152

AC:

215

AN:

1416

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.231

AC:

35089

AN:

152150

Hom.:

4940

Cov.:

AF XY:

0.232

AC XY:

17279

AN XY:

74370

show subpopulations

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:

AN:

290

European-Non Finnish (NFE)

AF:

0.155

AC:

10551

AN:

67974

Other (OTH)

AF:

0.229

AC:

485

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1307

2613

3920

5226

6533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.71

(source)

DANN

Benign

0.45

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over