Variant 10-97577837-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000370655.6(ANKRD2):c.125A>T(p.Asp42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,421,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANKRD2
ENST00000370655.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Variant links:

Genes affected

ANKRD2 (HGNC:495): (ankyrin repeat domain 2) This gene encodes a protein that belongs to the muscle ankyrin repeat protein (MARP) family. A similar gene in rodents is a component of a muscle stress response pathway and plays a role in the stretch-response associated with slow muscle function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ANKRD2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19304934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD2	NM_001346793.2 linkuse as main transcript	c.125A>T	p.Asp42Val	missense_variant	2/9	ENST00000370655.6	NP_001333722.1	A0A0A0MRN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRD2	ENST00000370655.6 linkuse as main transcript	c.125A>T	p.Asp42Val	missense_variant	2/9	1	NM_001346793.2	ENSP00000359689.1	A0A0A0MRN9
ANKRD2	ENST00000307518.9 linkuse as main transcript	c.206A>T	p.Asp69Val	missense_variant	2/9	1		ENSP00000306163.5	Q9GZV1-1
ANKRD2	ENST00000298808.9 linkuse as main transcript	c.206A>T	p.Asp69Val	missense_variant	2/8	1		ENSP00000298808.5	Q9GZV1-2
ANKRD2	ENST00000455090.1 linkuse as main transcript	c.125A>T	p.Asp42Val	missense_variant	2/8	1		ENSP00000403114.1	Q5T457

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1421480

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

702788

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.206A>T (p.D69V) alteration is located in exon 2 (coding exon 2) of the ANKRD2 gene. This alteration results from a A to T substitution at nucleotide position 206, causing the aspartic acid (D) at amino acid position 69 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.080

T;.;.;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.39

B;P;.;.

Vest4

0.25

MutPred

0.38

Loss of ubiquitination at K65 (P = 0.0524);Loss of ubiquitination at K65 (P = 0.0524);.;.;

MVP

0.84

MPC

0.52

ClinPred

0.93

GERP RS

4.7

Varity_R

0.27

gMVP

0.61

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over