Variant rs7094973 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001346793.2(ANKRD2):c.103G>A(p.Ala35Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,564,036 control chromosomes in the GnomAD database, including 338,443 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 24990 hom., cov: 31)

Exomes 𝑓: 0.66 ( 313453 hom. )

Consequence

ANKRD2
NM_001346793.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.69

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.7439586E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD2	NM_001346793.2 linkuse as main transcript	c.103G>A	p.Ala35Thr	missense_variant	2/9	ENST00000370655.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD2	ENST00000370655.6 linkuse as main transcript	c.103G>A	p.Ala35Thr	missense_variant	2/9	1	NM_001346793.2
ANKRD2	ENST00000307518.9 linkuse as main transcript	c.184G>A	p.Ala62Thr	missense_variant	2/9	1		P1	Q9GZV1-1
ANKRD2	ENST00000298808.9 linkuse as main transcript	c.184G>A	p.Ala62Thr	missense_variant	2/8	1			Q9GZV1-2
ANKRD2	ENST00000455090.1 linkuse as main transcript	c.103G>A	p.Ala35Thr	missense_variant	2/8	1

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

82978

AN:

151926

Hom.:

24991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.694

Gnomad OTH

AF:

0.584

GnomAD3 exomes

AF:

0.596

AC:

105130

AN:

176376

Hom.:

32653

AF XY:

0.598

AC XY:

55738

AN XY:

93250

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.621

Gnomad ASJ exome

AF:

0.680

Gnomad EAS exome

AF:

0.424

Gnomad SAS exome

AF:

0.508

Gnomad FIN exome

AF:

0.585

Gnomad NFE exome

AF:

0.688

Gnomad OTH exome

AF:

0.640

GnomAD4 exome

AF:

0.659

AC:

931011

AN:

1411992

Hom.:

313453

Cov.:

AF XY:

0.656

AC XY:

457445

AN XY:

697326

show subpopulations

Gnomad4 AFR exome

AF:

0.255

Gnomad4 AMR exome

AF:

0.623

Gnomad4 ASJ exome

AF:

0.685

Gnomad4 EAS exome

AF:

0.431

Gnomad4 SAS exome

AF:

0.505

Gnomad4 FIN exome

AF:

0.593

Gnomad4 NFE exome

AF:

0.696

Gnomad4 OTH exome

AF:

0.630

GnomAD4 genome

AF:

0.546

AC:

82985

AN:

152044

Hom.:

24990

Cov.:

AF XY:

0.541

AC XY:

40197

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.626

Gnomad4 ASJ

AF:

0.677

Gnomad4 EAS

AF:

0.432

Gnomad4 SAS

AF:

0.489

Gnomad4 FIN

AF:

0.577

Gnomad4 NFE

AF:

0.694

Gnomad4 OTH

AF:

0.583

Alfa

AF:

0.669

Hom.:

64804

Bravo

AF:

0.538

TwinsUK

AF:

0.696

AC:

2581

ALSPAC

AF:

0.697

AC:

2688

ESP6500AA

AF:

0.285

AC:

1255

ESP6500EA

AF:

0.703

AC:

6028

ExAC

AF:

0.530

AC:

58391

Asia WGS

AF:

0.434

AC:

1512

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

Cadd

Benign

0.049

Dann

Benign

0.46

DEOGEN2

Benign

0.042

T;.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.31

T;T;T;T

MetaRNN

Benign

0.0000037

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.40

N;N;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.17

N;N;N;N

REVEL

Benign

0.014

Sift

Benign

0.38

T;T;T;T

Sift4G

Benign

0.70

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.029

MPC

0.19

ClinPred

0.013

GERP RS

-7.9

Varity_R

0.026

gMVP

0.21

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over