10-97577815-G-T

Variant names:

• chr10-97577815-G-T
• rs7094973
• NM_001346793.2:c.103G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001346793.2(ANKRD2):​c.103G>T​(p.Ala35Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD2 NM_001346793.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 30 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05734083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD2	NM_001346793.2	c.103G>T	p.Ala35Ser	missense_variant	Exon 2 of 9	ENST00000370655.6	NP_001333722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD2	ENST00000370655.6	c.103G>T	p.Ala35Ser	missense_variant	Exon 2 of 9	1	NM_001346793.2	ENSP00000359689.1
ANKRD2	ENST00000307518.9	c.184G>T	p.Ala62Ser	missense_variant	Exon 2 of 9	1		ENSP00000306163.5
ANKRD2	ENST00000298808.9	c.184G>T	p.Ala62Ser	missense_variant	Exon 2 of 8	1		ENSP00000298808.5
ANKRD2	ENST00000455090.1	c.103G>T	p.Ala35Ser	missense_variant	Exon 2 of 8	1		ENSP00000403114.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1412674 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 697706

African (AFR) AF: 0.00 AC: 0 AN: 32866

American (AMR) AF: 0.00 AC: 0 AN: 36518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 37846

South Asian (SAS) AF: 0.00 AC: 0 AN: 80146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5092

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086552

Other (OTH) AF: 0.00 AC: 0 AN: 58568

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 91291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.022
DANN	Benign	0.46
DEOGEN2	Benign	0.027	T;.;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.34	T;T;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.057	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L;L;.;.
PhyloP100		-2.7
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.040	N;N;N;N
REVEL	Benign	0.0030
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.78	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.066
MutPred		0.21		Gain of phosphorylation at A62 (P = 0.0064);Gain of phosphorylation at A62 (P = 0.0064);.;.;
MVP		0.24
MPC		0.18
ClinPred		0.068	T
GERP RS		-7.9
Varity_R		0.038
gMVP		0.11
Mutation Taster		=97/3	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: rs7094973; hg19: chr10-99337572;