Variant 4-112904538-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000506722.5(ANK2):c.21+24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,444,442 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 9 hom. )

Consequence

ANK2
ENST00000506722.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.16

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 4-112904538-A-G is Benign according to our data. Variant chr4-112904538-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1195276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00743 (1131/152310) while in subpopulation AFR AF= 0.0252 (1048/41580). AF 95% confidence interval is 0.0239. There are 8 homozygotes in gnomad4. There are 549 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1131 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect
ANK2	NM_001127493.3 linkuse as main transcript	c.21+24A>G	intron_variant
ANK2	NM_001354239.2 linkuse as main transcript	c.21+24A>G	intron_variant
ANK2	NM_001354243.2 linkuse as main transcript	c.21+24A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Appris	UniProt
ANK2	ENST00000506722.5 linkuse as main transcript	c.21+24A>G	intron_variant	1		Q01484-5
ANK2	ENST00000503271.5 linkuse as main transcript	c.21+24A>G	intron_variant	2
ANK2	ENST00000503423.6 linkuse as main transcript	c.21+24A>G	intron_variant	5	A2

Frequencies

GnomAD3 genomes

AF:

0.00739

AC:

1125

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00182

AC:

233

AN:

127938

Hom.:

AF XY:

0.00147

AC XY:

100

AN XY:

67918

show subpopulations

Gnomad AFR exome

AF:

0.0265

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000303

Gnomad OTH exome

AF:

0.00111

GnomAD4 exome

AF:

0.000755

AC:

976

AN:

1292132

Hom.:

Cov.:

AF XY:

0.000652

AC XY:

417

AN XY:

639976

show subpopulations

Gnomad4 AFR exome

AF:

0.0247

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000866

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000123

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00743

AC:

1131

AN:

152310

Hom.:

Cov.:

AF XY:

0.00737

AC XY:

549

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0252

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.00866

Asia WGS

AF:

0.00175

AC:

AN:

3436

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.91

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over