10-90918983-AATAAATAAATATATATAT-A

Variant names:

• chr10-90918983-AATAAATAAATATATATAT-A
• rs72003210
• NM_014391.3:c.346-29_346-12delATATATATATTTATTTAT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_014391.3(ANKRD1):​c.346-29_346-12delATATATATATTTATTTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,408,210 control chromosomes in the GnomAD database, including 253,135 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.44 (14706 hom., cov: 0)
  • Exomes 𝑓: 0.59 (238429 hom.)
• Consequence: ANKRD1 NM_014391.3 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:7
• Conservation: PhyloP100: 3.19
• Publications: 2 publications found

Genes affected

ANKRD1 (HGNC:15819): (ankyrin repeat domain 1) The protein encoded by this gene is localized to the nucleus of endothelial cells and is induced by IL-1 and TNF-alpha stimulation. Studies in rat cardiomyocytes suggest that this gene functions as a transcription factor. Interactions between this protein and the sarcomeric proteins myopalladin and titin suggest that it may also be involved in the myofibrillar stretch-sensor system. [provided by RefSeq, Jul 2008]

ANKRD1 Gene-Disease associations (from GenCC):

• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 10-90918983-AATAAATAAATATATATAT-A is Benign according to our data. Variant chr10-90918983-AATAAATAAATATATATAT-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 301605.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD1	NM_014391.3	c.346-29_346-12delATATATATATTTATTTAT		intron_variant	Intron 3 of 8	ENST00000371697.4	NP_055206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD1	ENST00000371697.4	c.346-29_346-12delATATATATATTTATTTAT		intron_variant	Intron 3 of 8	1	NM_014391.3	ENSP00000360762.3

Frequencies

GnomAD3 genomes AF: 0.445 AC: 60452 AN: 135870 Hom.: 14703 Cov.: 0

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.458

GnomAD2 exomes AF: 0.560 AC: 119603 AN: 213642 AF XY: 0.556

Gnomad AFR exome AF: 0.430

Gnomad AMR exome AF: 0.609

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.543

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.574

Gnomad OTH exome AF: 0.564

GnomAD4 exome AF: 0.594 AC: 755978 AN: 1272300 Hom.: 238429 AF XY: 0.592 AC XY: 375536 AN XY: 634102

African (AFR) AF: 0.506 AC: 8270 AN: 16352

American (AMR) AF: 0.677 AC: 24888 AN: 36752

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 13276 AN: 23262

East Asian (EAS) AF: 0.597 AC: 16635 AN: 27848

South Asian (SAS) AF: 0.595 AC: 41170 AN: 69174

European-Finnish (FIN) AF: 0.595 AC: 26906 AN: 45254

Middle Eastern (MID) AF: 0.605 AC: 2878 AN: 4754

European-Non Finnish (NFE) AF: 0.593 AC: 591403 AN: 997272

Other (OTH) AF: 0.592 AC: 30552 AN: 51632

GnomAD4 genome AF: 0.445 AC: 60467 AN: 135910 Hom.: 14706 Cov.: 0 AF XY: 0.450 AC XY: 29624 AN XY: 65904

African (AFR) AF: 0.274 AC: 8751 AN: 31942

American (AMR) AF: 0.501 AC: 7100 AN: 14174

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1609 AN: 3400

East Asian (EAS) AF: 0.425 AC: 1911 AN: 4494

South Asian (SAS) AF: 0.462 AC: 2000 AN: 4328

European-Finnish (FIN) AF: 0.555 AC: 5039 AN: 9080

Middle Eastern (MID) AF: 0.438 AC: 119 AN: 272

European-Non Finnish (NFE) AF: 0.498 AC: 32558 AN: 65384

Other (OTH) AF: 0.460 AC: 888 AN: 1932

Alfa AF: 0.455 Hom.: 1570

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:7

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Dilated Cardiomyopathy, Dominant Uncertain:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital total pulmonary venous return anomaly Benign:2

Sep 06, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:1

Apr 25, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ANKRD1-related dilated cardiomyopathy Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ANKRD1-related disorder Benign:1

Jul 03, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Cardiovascular phenotype Benign:1

Sep 28, 2015

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs72003210; hg19: chr10-92678740; COSMIC: COSV106063358; COSMIC: COSV106063358;