10-97578382-C-G

Variant names:

• chr10-97578382-C-G
• rs751301897
• NM_001346793.2:c.332C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001346793.2(ANKRD2):​c.332C>G​(p.Pro111Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P111L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKRD2 NM_001346793.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40609118).

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.332C>G	p.Pro111Arg	missense	Exon 3 of 9	NP_001333722.1	A0A0A0MRN9
	ANKRD2	NM_001291218.2		c.671C>G	p.Pro224Arg	missense	Exon 3 of 9	NP_001278147.1
	ANKRD2	NM_020349.4		c.413C>G	p.Pro138Arg	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.332C>G	p.Pro111Arg	missense	Exon 3 of 9	ENSP00000359689.1	A0A0A0MRN9
	ANKRD2	ENST00000307518.9	TSL:1	c.413C>G	p.Pro138Arg	missense	Exon 3 of 9	ENSP00000306163.5	Q9GZV1-1
	ANKRD2	ENST00000298808.9	TSL:1	c.413C>G	p.Pro138Arg	missense	Exon 3 of 8	ENSP00000298808.5	Q9GZV1-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461588 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727096

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74280

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.089
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.3
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.16
Sift	Benign	0.036	D
Sift4G	Benign	0.072	T
Polyphen		0.91	P
Vest4		0.52
MutPred		0.23		Loss of glycosylation at P138 (P = 0.0162)
MVP		0.85
MPC		0.60
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.32
gMVP		0.56
Mutation Taster		=72/28	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: rs751301897; hg19: chr10-99338139;