GeneBe

rs776659587

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014391.3(ANKRD1):​c.222delA​(p.Lys74AsnfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,088 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ANKRD1
NM_014391.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.843

Publications

0 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD1NM_014391.3 linkc.222delA p.Lys74AsnfsTer2 frameshift_variant Exon 3 of 9 ENST00000371697.4 NP_055206.2 Q15327A0A384NYH5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD1ENST00000371697.4 linkc.222delA p.Lys74AsnfsTer2 frameshift_variant Exon 3 of 9 1 NM_014391.3 ENSP00000360762.3 Q15327

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1454088
Hom.:
0
Cov.:
32
AF XY:
0.00000415
AC XY:
3
AN XY:
723362
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33150
American (AMR)
AF:
0.00
AC:
0
AN:
44148
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26010
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39518
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85398
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50738
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5592
European-Non Finnish (NFE)
AF:
0.00000270
AC:
3
AN:
1109430
Other (OTH)
AF:
0.00
AC:
0
AN:
60104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs776659587; hg19: chr10-92679010; COSMIC: COSV63311106; COSMIC: COSV63311106; API