rs200310346

Variant names:

• chr10-97572774-C-T
• rs200310346
• ENST00000307518.9:c.67C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001291218.2(ANKRD2):​c.325C>T​(p.Pro109Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,599,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: ANKRD2 NM_001291218.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.496
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025706917).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291218.2. 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_001291218.2		c.325C>T	p.Pro109Ser	missense	Exon 1 of 9	NP_001278147.1
	ANKRD2	NM_020349.4		c.67C>T	p.Pro23Ser	missense	Exon 1 of 9	NP_065082.2
	ANKRD2	NM_001129981.3		c.67C>T	p.Pro23Ser	missense	Exon 1 of 8	NP_001123453.1	Q9GZV1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD2	ENST00000307518.9	TSL:1	c.67C>T	p.Pro23Ser	missense	Exon 1 of 9	ENSP00000306163.5	Q9GZV1-1
	ANKRD2	ENST00000298808.9	TSL:1	c.67C>T	p.Pro23Ser	missense	Exon 1 of 8	ENSP00000298808.5	Q9GZV1-2
	ANKRD2	ENST00000960741.1		c.-15C>T		5_prime_UTR	Exon 1 of 10	ENSP00000630800.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000164 AC: 36 AN: 219664 AF XY: 0.000169

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000758

Gnomad NFE exome AF: 0.000153

Gnomad OTH exome AF: 0.000367

GnomAD4 exome AF: 0.000223 AC: 323 AN: 1446714 Hom.: 0 Cov.: 32 AF XY: 0.000238 AC XY: 171 AN XY: 718050

African (AFR) AF: 0.0000300 AC: 1 AN: 33312

American (AMR) AF: 0.000142 AC: 6 AN: 42352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25764

East Asian (EAS) AF: 0.00 AC: 0 AN: 39034

South Asian (SAS) AF: 0.00 AC: 0 AN: 83056

European-Finnish (FIN) AF: 0.000861 AC: 45 AN: 52254

Middle Eastern (MID) AF: 0.000578 AC: 3 AN: 5194

European-Non Finnish (NFE) AF: 0.000231 AC: 255 AN: 1105974

Other (OTH) AF: 0.000217 AC: 13 AN: 59774

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74510

African (AFR) AF: 0.0000481 AC: 2 AN: 41588

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68024

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00161 Hom.: 1

Bravo AF: 0.000128

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000116 AC: 14

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	Benign	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.50
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.10
Sift	Benign	0.053	T
Sift4G	Benign	0.52	T
Polyphen		0.18	B
Vest4		0.25
MVP		0.63
MPC		0.21
ClinPred		0.045	T
GERP RS		4.8
PromoterAI		-0.11	Neutral
Varity_R		0.057
gMVP		0.20
Mutation Taster		=94/6	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: rs200310346; hg19: chr10-99332531;