10-97578273-C-G

Variant names:

• chr10-97578273-C-G
• rs2040851526
• NM_001346793.2:c.223C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001346793.2(ANKRD2):​c.223C>G​(p.Leu75Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.39
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346793.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD2	NM_001346793.2	MANE Select	c.223C>G	p.Leu75Val	missense	Exon 3 of 9	NP_001333722.1	A0A0A0MRN9
	ANKRD2	NM_001291218.2		c.562C>G	p.Leu188Val	missense	Exon 3 of 9	NP_001278147.1
	ANKRD2	NM_020349.4		c.304C>G	p.Leu102Val	missense	Exon 3 of 9	NP_065082.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD2	ENST00000370655.6	TSL:1 MANE Select	c.223C>G	p.Leu75Val	missense	Exon 3 of 9	ENSP00000359689.1	A0A0A0MRN9
	ANKRD2	ENST00000307518.9	TSL:1	c.304C>G	p.Leu102Val	missense	Exon 3 of 9	ENSP00000306163.5	Q9GZV1-1
	ANKRD2	ENST00000298808.9	TSL:1	c.304C>G	p.Leu102Val	missense	Exon 3 of 8	ENSP00000298808.5	Q9GZV1-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.19	T
Polyphen		0.99	D
Vest4		0.58
MutPred		0.23		Gain of MoRF binding (P = 0.109)
MVP		0.77
MPC		0.78
ClinPred		0.95	D
GERP RS		4.4
Varity_R		0.25
gMVP		0.69
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs2040851526; hg19: chr10-99338030;