dbSNP rs1032913: ANK2:c.21+113430A>G (chr4-113017944-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_001386142.1(ANK2):c.21+113430A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,196 control chromosomes in the GnomAD database, including 49,934 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 0.81 ( 49934 hom., cov: 33)

Consequence

ANK2
NM_001386142.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

1 publications found

Variant links:

Genes affected

ANK2 (HGNC:493): (ankyrin 2) This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. The protein encoded by this gene is required for targeting and stability of Na/Ca exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4 and cardiac arrhythmia syndrome. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2011]

ANK2 links:

ANK2-AS1 (HGNC:40076): (ANK2 antisense RNA 1)

ANK2-AS1 links:

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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=-0.93).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386142.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
ANK2	NM_001386142.1	c.21+113430A>G	intron	N/A	NP_001373071.1
ANK2	NM_001386143.1	c.21+113430A>G	intron	N/A	NP_001373072.1	A0A5F9ZGZ1
ANK2	NM_001386186.2	c.73-156472A>G	intron	N/A	NP_001373115.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANK2	ENST00000506722.5	TSL:1	c.21+113430A>G	intron	N/A	ENSP00000421067.1	Q01484-5
ANK2	ENST00000672209.1		c.21+113430A>G	intron	N/A	ENSP00000499982.1	A0A5F9ZH30
ANK2	ENST00000673298.1		c.21+113430A>G	intron	N/A	ENSP00000500245.1	A0A5F9ZHE4

Frequencies

GnomAD3 genomes

AF:

0.810

AC:

123233

AN:

152078

Hom.:

49890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.825

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.859

Gnomad ASJ

AF:

0.802

Gnomad EAS

AF:

0.865

Gnomad SAS

AF:

0.865

Gnomad FIN

AF:

0.751

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.793

Gnomad OTH

AF:

0.818

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

GnomAD4 genome

AF:

0.810

AC:

123338

AN:

152196

Hom.:

49934

Cov.:

AF XY:

0.812

AC XY:

60398

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.825

AC:

34247

AN:

41536

American (AMR)

AF:

0.860

AC:

13149

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.802

AC:

2781

AN:

3468

East Asian (EAS)

AF:

0.865

AC:

4476

AN:

5176

South Asian (SAS)

AF:

0.866

AC:

4181

AN:

4828

European-Finnish (FIN)

AF:

0.751

AC:

7944

AN:

10578

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.793

AC:

53907

AN:

67996

Other (OTH)

AF:

0.820

AC:

1734

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1256

2511

3767

5022

6278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<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:

0.792

Hom.:

21254

Bravo

AF:

0.820

Asia WGS

AF:

0.878

AC:

3055

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.79

(source)

DANN

Benign

0.47

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over