rs2275588

Positions:

• chr10-97581428-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370655.6(ANKRD2):​c.654+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 1,613,252 control chromosomes in the GnomAD database, including 7,407 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (3624 hom., cov: 33)
  • Exomes 𝑓: 0.026 (3783 hom.)
• Consequence: ANKRD2 ENST00000370655.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD2	NM_001346793.2	c.654+14A>G		intron_variant		ENST00000370655.6	NP_001333722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD2	ENST00000370655.6	c.654+14A>G		intron_variant		1	NM_001346793.2	ENSP00000359689
ANKRD2	ENST00000298808.9	c.735+14A>G		intron_variant		1		ENSP00000298808
ANKRD2	ENST00000307518.9	c.735+14A>G		intron_variant		1		ENSP00000306163	P1
ANKRD2	ENST00000455090.1	c.654+14A>G		intron_variant		1		ENSP00000403114

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19622 AN: 152086 Hom.: 3596 Cov.: 33

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.0583

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.00860

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.0570 AC: 14305 AN: 250958 Hom.: 1681 AF XY: 0.0484 AC XY: 6570 AN XY: 135674

Gnomad AFR exome AF: 0.415

Gnomad AMR exome AF: 0.0750

Gnomad ASJ exome AF: 0.0260

Gnomad EAS exome AF: 0.0978

Gnomad SAS exome AF: 0.0509

Gnomad FIN exome AF: 0.00430

Gnomad NFE exome AF: 0.00930

Gnomad OTH exome AF: 0.0381

GnomAD4 exome AF: 0.0256 AC: 37471 AN: 1461048 Hom.: 3783 Cov.: 30 AF XY: 0.0250 AC XY: 18203 AN XY: 726880

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.0731

Gnomad4 ASJ exome AF: 0.0264

Gnomad4 EAS exome AF: 0.0820

Gnomad4 SAS exome AF: 0.0502

Gnomad4 FIN exome AF: 0.00463

Gnomad4 NFE exome AF: 0.00730

Gnomad4 OTH exome AF: 0.0480

GnomAD4 genome AF: 0.129 AC: 19700 AN: 152204 Hom.: 3624 Cov.: 33 AF XY: 0.126 AC XY: 9377 AN XY: 74410

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.0917

Gnomad4 SAS AF: 0.0573

Gnomad4 FIN AF: 0.00556

Gnomad4 NFE AF: 0.00860

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0848 Hom.: 492

Bravo AF: 0.149

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs2275588; hg19: chr10-99341185;