Genetic Variant ANKRD2:c.-86_-84delGGC (chr10-97572621-TGGC-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBA1

The NM_001291218.2(ANKRD2):c.173_175delGGC(p.Trp58_Pro59delinsSer) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 1,472,248 control chromosomes in the GnomAD database, including 3,518 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.090 ( 1767 hom., cov: 32)

Exomes 𝑓: 0.016 ( 1751 hom. )

Consequence

ANKRD2
NM_001291218.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.44

Variant links:

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]

ANKRD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001291218.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 10-97572621-TGGC-T is Benign according to our data. Variant chr10-97572621-TGGC-T is described in ClinVar as [Benign]. Clinvar id is 776534.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD2	NM_001346793.2 link	c.-167_-165delGGC		upstream_gene_variant		ENST00000370655.6	NP_001333722.1	A0A0A0MRN9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANKRD2	ENST00000307518 link	c.-86_-84delGGC	5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000306163.5	Q9GZV1-1
ANKRD2	ENST00000298808 link	c.-86_-84delGGC	5_prime_UTR_variant	Exon 1 of 8	1		ENSP00000298808.5	Q9GZV1-2
ANKRD2	ENST00000370655.6 link	c.-167_-165delGGC	upstream_gene_variant		1	NM_001346793.2	ENSP00000359689.1	A0A0A0MRN9
ANKRD2	ENST00000455090.1 link	c.-167_-165delGGC	upstream_gene_variant		1		ENSP00000403114.1	Q5T457

Frequencies

GnomAD3 genomes

AF:

0.0896

AC:

13631

AN:

152098

Hom.:

1754

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0497

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.0793

Gnomad SAS

AF:

0.0283

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00403

Gnomad OTH

AF:

0.0718

GnomAD4 exome

AF:

0.0158

AC:

20887

AN:

1320032

Hom.:

1751

AF XY:

0.0154

AC XY:

9896

AN XY:

643906

show subpopulations

Gnomad4 AFR exome

AF:

0.308

Gnomad4 AMR exome

AF:

0.0634

Gnomad4 ASJ exome

AF:

0.0205

Gnomad4 EAS exome

AF:

0.0655

Gnomad4 SAS exome

AF:

0.0247

Gnomad4 FIN exome

AF:

0.000433

Gnomad4 NFE exome

AF:

0.00319

Gnomad4 OTH exome

AF:

0.0337

GnomAD4 genome

AF:

0.0899

AC:

13677

AN:

152216

Hom.:

1767

Cov.:

AF XY:

0.0875

AC XY:

6512

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.286

Gnomad4 AMR

AF:

0.0496

Gnomad4 ASJ

AF:

0.0185

Gnomad4 EAS

AF:

0.0793

Gnomad4 SAS

AF:

0.0286

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00403

Gnomad4 OTH

AF:

0.0710

Alfa

AF:

0.0541

Hom.:

120

Bravo

AF:

0.105

Asia WGS

AF:

0.0540

AC:

189

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over