Variant 10-97583589-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000370655.6(ANKRD2):c.866C>T(p.Pro289Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000524 in 1,603,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

ANKRD2
ENST00000370655.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD2	NM_001346793.2 linkuse as main transcript	c.866C>T	p.Pro289Leu	missense_variant	9/9	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.866C>T	p.Pro289Leu	missense_variant	9/9	1	NM_001346793.2	ENSP00000359689.1	A0A0A0MRN9
ANKRD2	ENST00000307518.9 linkuse as main transcript	c.947C>T	p.Pro316Leu	missense_variant	9/9	1		ENSP00000306163.5	Q9GZV1-1
ANKRD2	ENST00000298808.9 linkuse as main transcript	c.848C>T	p.Pro283Leu	missense_variant	8/8	1		ENSP00000298808.5	Q9GZV1-2
ANKRD2	ENST00000455090.1 linkuse as main transcript	c.767C>T	p.Pro256Leu	missense_variant	8/8	1		ENSP00000403114.1	Q5T457

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000354

AC:

AN:

226188

Hom.:

AF XY:

0.0000244

AC XY:

AN XY:

123184

show subpopulations

Gnomad AFR exome

AF:

0.000220

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000500

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000496

AC:

AN:

1451228

Hom.:

Cov.:

AF XY:

0.0000430

AC XY:

AN XY:

720928

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000578

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000684

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000495

AC:

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

Mar 08, 2024

The c.947C>T (p.P316L) alteration is located in exon 9 (coding exon 9) of the ANKRD2 gene. This alteration results from a C to T substitution at nucleotide position 947, causing the proline (P) at amino acid position 316 to be replaced by a leucine (L). 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

0.94

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.;.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Uncertain

-0.034

MutationAssessor

Uncertain

2.1

M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-8.2

D;D;D;D

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.92

MVP

0.86

MPC

0.79

ClinPred

0.68

GERP RS

5.7

Varity_R

0.84

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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