Variant 10-97580862-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001346793.2(ANKRD2):c.464G>A(p.Arg155Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000491 in 1,610,486 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

ANKRD2
NM_001346793.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.52

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD2	NM_001346793.2 linkuse as main transcript	c.464G>A	p.Arg155Gln	missense_variant	5/9	ENST00000370655.6	NP_001333722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD2	ENST00000370655.6 linkuse as main transcript	c.464G>A	p.Arg155Gln	missense_variant	5/9	1	NM_001346793.2	ENSP00000359689
ANKRD2	ENST00000307518.9 linkuse as main transcript	c.545G>A	p.Arg182Gln	missense_variant	5/9	1		ENSP00000306163	P1	Q9GZV1-1
ANKRD2	ENST00000298808.9 linkuse as main transcript	c.545G>A	p.Arg182Gln	missense_variant	5/8	1		ENSP00000298808		Q9GZV1-2
ANKRD2	ENST00000455090.1 linkuse as main transcript	c.464G>A	p.Arg155Gln	missense_variant	5/8	1		ENSP00000403114

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000409

AC:

AN:

244654

Hom.:

AF XY:

0.0000454

AC XY:

AN XY:

132218

show subpopulations

Gnomad AFR exome

AF:

0.000192

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000553

Gnomad SAS exome

AF:

0.0000676

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000361

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000521

AC:

AN:

1458214

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

725002

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000703

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 11, 2021

The c.545G>A (p.R182Q) alteration is located in exon 5 (coding exon 5) of the ANKRD2 gene. This alteration results from a G to A substitution at nucleotide position 545, causing the arginine (R) at amino acid position 182 to be replaced by a glutamine (Q). 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

Pathogenic

0.84

BayesDel_addAF

Benign

0.0027

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;.;.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.070

MetaRNN

Uncertain

0.66

D;D;D;D

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.4

L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.7

D;D;D;D

REVEL

Uncertain

0.43

Sift

Benign

0.043

D;D;D;D

Sift4G

Uncertain

0.035

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.73

MVP

0.85

MPC

0.84

ClinPred

0.68

GERP RS

5.4

Varity_R

0.33

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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