Genetic Variant ANK2:c.72+82800T>C (chr4-112789017-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001386186.2(ANK2):c.72+82800T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 517,422 control chromosomes in the GnomAD database, including 22,738 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 0.31 ( 8634 hom., cov: 32)

Exomes 𝑓: 0.25 ( 14104 hom. )

Consequence

ANK2
NM_001386186.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.133

Publications

2 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:

RPL7AP30 (HGNC:35757): (ribosomal protein L7a pseudogene 30)

RPL7AP30 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
ANK2	NM_001386186.2 link	c.72+82800T>C	intron_variant	Intron 1 of 46	NP_001373115.1
ANK2	NM_001386148.2 link	c.72+82800T>C	intron_variant	Intron 1 of 45	NP_001373077.1
ANK2	NM_001386187.2 link	c.72+82800T>C	intron_variant	Intron 1 of 42	NP_001373116.1
ANK2	NM_001354269.3 link	c.72+82800T>C	intron_variant	Intron 1 of 43	NP_001341198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL7AP30	ENST00000482859.1 link	n.-139A>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47045

AN:

151806

Hom.:

8614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.474

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.261

GnomAD4 exome

AF:

0.248

AC:

90775

AN:

365498

Hom.:

14104

AF XY:

0.246

AC XY:

46641

AN XY:

189752

show subpopulations

African (AFR)

AF:

0.462

AC:

5018

AN:

10866

American (AMR)

AF:

0.384

AC:

5501

AN:

14314

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

1373

AN:

11930

East Asian (EAS)

AF:

0.574

AC:

16375

AN:

28510

South Asian (SAS)

AF:

0.278

AC:

6488

AN:

23380

European-Finnish (FIN)

AF:

0.206

AC:

5204

AN:

25210

Middle Eastern (MID)

AF:

0.173

AC:

293

AN:

1690

European-Non Finnish (NFE)

AF:

0.199

AC:

45218

AN:

227428

Other (OTH)

AF:

0.239

AC:

5305

AN:

22170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2909

5818

8727

11636

14545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.310

AC:

47122

AN:

151924

Hom.:

8634

Cov.:

AF XY:

0.313

AC XY:

23256

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.474

AC:

19635

AN:

41382

American (AMR)

AF:

0.355

AC:

5415

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

434

AN:

3470

East Asian (EAS)

AF:

0.581

AC:

3004

AN:

5168

South Asian (SAS)

AF:

0.321

AC:

1549

AN:

4820

European-Finnish (FIN)

AF:

0.207

AC:

2184

AN:

10546

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14079

AN:

67966

Other (OTH)

AF:

0.260

AC:

550

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1507

3013

4520

6026

7533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<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:

0.241

Hom.:

19159

Bravo

AF:

0.331

Asia WGS

AF:

0.422

AC:

1465

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.7

(source)

DANN

Benign

0.77

PhyloP100

0.13

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over