chr10-97572842-C-G

Position:

• chr10-97572842-C-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.54C>G​(p.Ile18Met) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD2 NM_001346793.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.60

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=0.23793802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD2	NM_001346793.2	c.54C>G	p.Ile18Met	missense_variant	1/9	ENST00000370655.6	NP_001333722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD2	ENST00000370655.6	c.54C>G	p.Ile18Met	missense_variant	1/9	1	NM_001346793.2	ENSP00000359689.1
ANKRD2	ENST00000307518.9	c.135C>G	p.Ile45Met	missense_variant	1/9	1		ENSP00000306163.5
ANKRD2	ENST00000298808.9	c.135C>G	p.Ile45Met	missense_variant	1/8	1		ENSP00000298808.5
ANKRD2	ENST00000455090.1	c.54C>G	p.Ile18Met	missense_variant	1/8	1		ENSP00000403114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Mar 25, 2024

The c.135C>G (p.I45M) alteration is located in exon 1 (coding exon 1) of the ANKRD2 gene. This alteration results from a C to G substitution at nucleotide position 135, causing the isoleucine (I) at amino acid position 45 to be replaced by a methionine (M). 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	0.24
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	8.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T;.;.;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.75	T;T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.3	M;M;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.64	N;N;N;N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.43
MutPred		0.41		Gain of disorder (P = 0.0308);Gain of disorder (P = 0.0308);.;.;
MVP		0.67
MPC		0.76
ClinPred		0.94	D
GERP RS		-4.7
Varity_R		0.34
gMVP		0.31

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: chr10-99332599;