10-97578541-A-T

Position:

• chr10-97578541-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001346793.2(ANKRD2):​c.392A>T​(p.Glu131Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ANKRD2 NM_001346793.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3789421).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD2	NM_001346793.2	c.392A>T	p.Glu131Val	missense_variant	4/9	ENST00000370655.6	NP_001333722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD2	ENST00000370655.6	c.392A>T	p.Glu131Val	missense_variant	4/9	1	NM_001346793.2	ENSP00000359689
ANKRD2	ENST00000307518.9	c.473A>T	p.Glu158Val	missense_variant	4/9	1		ENSP00000306163	P1
ANKRD2	ENST00000298808.9	c.473A>T	p.Glu158Val	missense_variant	4/8	1		ENSP00000298808
ANKRD2	ENST00000455090.1	c.392A>T	p.Glu131Val	missense_variant	4/8	1		ENSP00000403114

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2023

The c.473A>T (p.E158V) alteration is located in exon 4 (coding exon 4) of the ANKRD2 gene. This alteration results from a A to T substitution at nucleotide position 473, causing the glutamic acid (E) at amino acid position 158 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	0.44
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.4	L;L;.;.
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.2	D;D;D;D
REVEL	Benign	0.29
Sift	Benign	0.032	D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.77	P;D;.;.
Vest4		0.41
MutPred		0.41		Loss of disorder (P = 0.0202);Loss of disorder (P = 0.0202);.;.;
MVP		0.87
MPC		0.83
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.51
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr10-99338298;