rs2275588

Variant names:

• chr10-97581428-A-G
• rs2275588
• NM_001346793.2:c.654+14A>G

Variant summary

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

The NM_001346793.2(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 NM_001346793.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 5 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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD2	NM_001346793.2	MANE Select	c.654+14A>G		intron	N/A	NP_001333722.1
	ANKRD2	NM_001291218.2		c.993+14A>G		intron	N/A	NP_001278147.1
	ANKRD2	NM_020349.4		c.735+14A>G		intron	N/A	NP_065082.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD2	ENST00000370655.6	TSL:1 MANE Select	c.654+14A>G		intron	N/A	ENSP00000359689.1
	ANKRD2	ENST00000307518.9	TSL:1	c.735+14A>G		intron	N/A	ENSP00000306163.5
	ANKRD2	ENST00000298808.9	TSL:1	c.735+14A>G		intron	N/A	ENSP00000298808.5

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

GnomAD2 exomes AF: 0.0570 AC: 14305 AN: 250958 AF XY: 0.0484

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 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

African (AFR) AF: 0.428 AC: 14310 AN: 33440

American (AMR) AF: 0.0731 AC: 3263 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.0264 AC: 689 AN: 26112

East Asian (EAS) AF: 0.0820 AC: 3253 AN: 39694

South Asian (SAS) AF: 0.0502 AC: 4326 AN: 86204

European-Finnish (FIN) AF: 0.00463 AC: 247 AN: 53374

Middle Eastern (MID) AF: 0.0640 AC: 369 AN: 5764

European-Non Finnish (NFE) AF: 0.00730 AC: 8119 AN: 1111442

Other (OTH) AF: 0.0480 AC: 2895 AN: 60356

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

African (AFR) AF: 0.409 AC: 16976 AN: 41484

American (AMR) AF: 0.0649 AC: 993 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3470

East Asian (EAS) AF: 0.0917 AC: 475 AN: 5180

South Asian (SAS) AF: 0.0573 AC: 277 AN: 4830

European-Finnish (FIN) AF: 0.00556 AC: 59 AN: 10616

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.00860 AC: 585 AN: 68016

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.0702 Hom.: 2793

Bravo AF: 0.149

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.54
PhyloP100		0.074
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: rs2275588; hg19: chr10-99341185; COSMIC: COSV107325306; COSMIC: COSV107325306;