Variant 4-112904455-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000506722.5(ANK2):c.-39G>C variant causes a splice region, 5 prime UTR change. The variant allele was found at a frequency of 0.000753 in 1,429,550 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00085 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00074 ( 8 hom. )

Consequence

ANK2
ENST00000506722.5 splice_region, 5_prime_UTR

Scores

Splicing: ADA: 0.7931

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.71

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.21).

BP6

Variant 4-112904455-G-C is Benign according to our data. Variant chr4-112904455-G-C is described in ClinVar as [Benign]. Clinvar id is 2655031.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 129 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
ANK2	NM_001127493.3 linkuse as main transcript	c.-39G>C	splice_region_variant, 5_prime_UTR_variant	2/47
ANK2	NM_001354239.2 linkuse as main transcript	c.-39G>C	splice_region_variant, 5_prime_UTR_variant	2/49
ANK2	NM_001354243.2 linkuse as main transcript	c.-39G>C	splice_region_variant, 5_prime_UTR_variant	2/47

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Appris	UniProt
ANK2	ENST00000506722.5 linkuse as main transcript	c.-39G>C	splice_region_variant, 5_prime_UTR_variant	2/47	1		Q01484-5
ANK2	ENST00000503271.5 linkuse as main transcript	c.-39G>C	splice_region_variant, 5_prime_UTR_variant	2/31	2
ANK2	ENST00000503423.6 linkuse as main transcript	c.-39G>C	splice_region_variant, 5_prime_UTR_variant	2/46	5	A2

Frequencies

GnomAD3 genomes

AF:

0.000849

AC:

129

AN:

151934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.0234

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00193

AC:

255

AN:

132364

Hom.:

AF XY:

0.00198

AC XY:

139

AN XY:

70244

show subpopulations

Gnomad AFR exome

AF:

0.000287

Gnomad AMR exome

AF:

0.0000547

Gnomad ASJ exome

AF:

0.0257

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000234

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000611

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.000741

AC:

947

AN:

1277500

Hom.:

Cov.:

AF XY:

0.000762

AC XY:

483

AN XY:

633550

show subpopulations

Gnomad4 AFR exome

AF:

0.000107

Gnomad4 AMR exome

AF:

0.0000682

Gnomad4 ASJ exome

AF:

0.0261

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000160

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.000848

AC:

129

AN:

152050

Hom.:

Cov.:

AF XY:

0.000834

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.0234

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.00479

Hom.:

Bravo

AF:

0.000929

Asia WGS

AF:

0.000582

AC:

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

ANK2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.79

dbscSNV1_RF

Benign

0.58

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