NM_001346793.2:c.103G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346793.2(ANKRD2):​c.103G>A​(p.Ala35Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,564,036 control chromosomes in the GnomAD database, including 338,443 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.55 (24990 hom., cov: 31)
  • Exomes 𝑓: 0.66 (313453 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.7439586E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD2	NM_001346793.2	c.103G>A	p.Ala35Thr	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>A	p.Ala35Thr	missense_variant	Exon 2 of 9	1	NM_001346793.2	ENSP00000359689.1
ANKRD2	ENST00000307518.9	c.184G>A	p.Ala62Thr	missense_variant	Exon 2 of 9	1		ENSP00000306163.5
ANKRD2	ENST00000298808.9	c.184G>A	p.Ala62Thr	missense_variant	Exon 2 of 8	1		ENSP00000298808.5
ANKRD2	ENST00000455090.1	c.103G>A	p.Ala35Thr	missense_variant	Exon 2 of 8	1		ENSP00000403114.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82978 AN: 151926 Hom.: 24991 Cov.: 31

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.584

GnomAD2 exomes AF: 0.596 AC: 105130 AN: 176376 AF XY: 0.598

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.621

Gnomad ASJ exome AF: 0.680

Gnomad EAS exome AF: 0.424

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.688

Gnomad OTH exome AF: 0.640

GnomAD4 exome AF: 0.659 AC: 931011 AN: 1411992 Hom.: 313453 Cov.: 41 AF XY: 0.656 AC XY: 457445 AN XY: 697326

African (AFR) AF: 0.255 AC: 8373 AN: 32848

American (AMR) AF: 0.623 AC: 22751 AN: 36492

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 17251 AN: 25166

East Asian (EAS) AF: 0.431 AC: 16313 AN: 37814

South Asian (SAS) AF: 0.505 AC: 40465 AN: 80102

European-Finnish (FIN) AF: 0.593 AC: 29580 AN: 49850

Middle Eastern (MID) AF: 0.617 AC: 3141 AN: 5090

European-Non Finnish (NFE) AF: 0.696 AC: 756251 AN: 1086094

Other (OTH) AF: 0.630 AC: 36886 AN: 58536

GnomAD4 genome AF: 0.546 AC: 82985 AN: 152044 Hom.: 24990 Cov.: 31 AF XY: 0.541 AC XY: 40197 AN XY: 74344

African (AFR) AF: 0.275 AC: 11391 AN: 41476

American (AMR) AF: 0.626 AC: 9575 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2351 AN: 3472

East Asian (EAS) AF: 0.432 AC: 2220 AN: 5144

South Asian (SAS) AF: 0.489 AC: 2359 AN: 4822

European-Finnish (FIN) AF: 0.577 AC: 6100 AN: 10578

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47135 AN: 67942

Other (OTH) AF: 0.583 AC: 1230 AN: 2110

Alfa AF: 0.663 Hom.: 91291

Bravo AF: 0.538

TwinsUK AF: 0.696 AC: 2581

ALSPAC AF: 0.697 AC: 2688

ESP6500AA AF: 0.285 AC: 1255

ESP6500EA AF: 0.703 AC: 6028

ExAC AF: 0.530 AC: 58391

Asia WGS AF: 0.434 AC: 1512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.049
DANN	Benign	0.46
DEOGEN2	Benign	0.042	T;.;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.31	T;T;T;T
MetaRNN	Benign	0.0000037	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.40	N;N;.;.
PhyloP100		-2.7
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.17	N;N;N;N
REVEL	Benign	0.014
Sift	Benign	0.38	T;T;T;T
Sift4G	Benign	0.70	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.029
MPC		0.19
ClinPred		0.013	T
GERP RS		-7.9
Varity_R		0.026
gMVP		0.21
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV53967763;