Genetic Variant NM_183377.2:c.1195+12G>A (chr17-33025914-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_183377.2(ASIC2):c.1195+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,608,346 control chromosomes in the GnomAD database, including 96 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 0.0081 ( 5 hom., cov: 32)

Exomes 𝑓: 0.011 ( 91 hom. )

Consequence

ASIC2
NM_183377.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.787

Publications

4 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS2

High AC in GnomAd4 at 1227 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2 link	c.1195+12G>A		intron_variant	Intron 5 of 9	ENST00000225823.7	NP_899233.1	Q16515-2
ASIC2	NM_001094.5 link	c.1042+12G>A		intron_variant	Intron 5 of 9		NP_001085.2	Q16515-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASIC2	ENST00000225823.7 link	c.1195+12G>A	intron_variant	Intron 5 of 9	1	NM_183377.2	ENSP00000225823.2	Q16515-2
ASIC2	ENST00000359872.6 link	c.1042+12G>A	intron_variant	Intron 5 of 9	1		ENSP00000352934.6	Q16515-1
ASIC2	ENST00000448983.1 link	n.600+12G>A	intron_variant	Intron 6 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.00807

AC:

1227

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00729

AC:

1788

AN:

245166

AF XY:

0.00740

show subpopulations

Gnomad AFR exome

AF:

0.00263

Gnomad AMR exome

AF:

0.00745

Gnomad ASJ exome

AF:

0.00421

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00761

GnomAD4 exome

AF:

0.0108

AC:

15734

AN:

1456102

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

7571

AN XY:

724316

show subpopulations

African (AFR)

AF:

0.00205

AC:

AN:

33124

American (AMR)

AF:

0.00817

AC:

357

AN:

43716

Ashkenazi Jewish (ASJ)

AF:

0.00453

AC:

117

AN:

25840

East Asian (EAS)

AF:

0.0000763

AC:

AN:

39314

South Asian (SAS)

AF:

0.000504

AC:

AN:

85286

European-Finnish (FIN)

AF:

0.00193

AC:

103

AN:

53334

Middle Eastern (MID)

AF:

0.00261

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0131

AC:

14484

AN:

1109620

Other (OTH)

AF:

0.00905

AC:

544

AN:

60130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

701

1402

2104

2805

3506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.00806

AC:

1227

AN:

152244

Hom.:

Cov.:

AF XY:

0.00793

AC XY:

590

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00270

AC:

112

AN:

41552

American (AMR)

AF:

0.0141

AC:

215

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5158

South Asian (SAS)

AF:

0.000623

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0123

AC:

834

AN:

68020

Other (OTH)

AF:

0.0109

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

136

204

272

340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00481

Hom.:

Bravo

AF:

0.00920

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.4

(source)

DANN

Benign

0.51

PhyloP100

0.79

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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