10-97572814-A-G

Variant names:

• chr10-97572814-A-G
• NM_001346793.2:c.26A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001346793.2(ANKRD2):​c.26A>G​(p.Glu9Gly) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E9K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD2 NM_001346793.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.337

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24481243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD2	NM_001346793.2	c.26A>G	p.Glu9Gly	missense_variant	Exon 1 of 9	ENST00000370655.6	NP_001333722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD2	ENST00000370655.6	c.26A>G	p.Glu9Gly	missense_variant	Exon 1 of 9	1	NM_001346793.2	ENSP00000359689.1
ANKRD2	ENST00000307518.9	c.107A>G	p.Glu36Gly	missense_variant	Exon 1 of 9	1		ENSP00000306163.5
ANKRD2	ENST00000298808.9	c.107A>G	p.Glu36Gly	missense_variant	Exon 1 of 8	1		ENSP00000298808.5
ANKRD2	ENST00000455090.1	c.26A>G	p.Glu9Gly	missense_variant	Exon 1 of 8	1		ENSP00000403114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1419456 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 702010

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.107A>G (p.E36G) alteration is located in exon 1 (coding exon 1) of the ANKRD2 gene. This alteration results from a A to G substitution at nucleotide position 107, causing the glutamic acid (E) at amino acid position 36 to be replaced by a glycine (G). 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	Benign	0.12
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T;.;.;T
Eigen	Benign	-0.015
Eigen_PC	Benign	0.054
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M;M;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.61	P;P;.;.
Vest4		0.22
MutPred		0.28		Gain of catalytic residue at E36 (P = 0.0057);Gain of catalytic residue at E36 (P = 0.0057);.;.;
MVP		0.85
MPC		0.41
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.13
gMVP		0.15

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.

Other links and lift over

hg19: chr10-99332571;