10-97578505-C-T

Position:

• chr10-97578505-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001346793.2(ANKRD2):​c.356C>T​(p.Pro119Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00629 in 1,585,216 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0065 (28 hom.)
• Consequence: ANKRD2 NM_001346793.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.50

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0077142417).
• BP6: Variant 10-97578505-C-T is Benign according to our data. Variant chr10-97578505-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-97578505-C-T is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD2	NM_001346793.2	c.356C>T	p.Pro119Leu	missense_variant	4/9	ENST00000370655.6	NP_001333722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD2	ENST00000370655.6	c.356C>T	p.Pro119Leu	missense_variant	4/9	1	NM_001346793.2	ENSP00000359689
ANKRD2	ENST00000307518.9	c.437C>T	p.Pro146Leu	missense_variant	4/9	1		ENSP00000306163	P1
ANKRD2	ENST00000298808.9	c.437C>T	p.Pro146Leu	missense_variant	4/8	1		ENSP00000298808
ANKRD2	ENST00000455090.1	c.356C>T	p.Pro119Leu	missense_variant	4/8	1		ENSP00000403114

Frequencies

GnomAD3 genomes AF: 0.00459 AC: 698 AN: 152182 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00747

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00403 AC: 804 AN: 199564 Hom.: 2 AF XY: 0.00411 AC XY: 440 AN XY: 107102

Gnomad AFR exome AF: 0.000575

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.000330

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000227

Gnomad FIN exome AF: 0.00647

Gnomad NFE exome AF: 0.00695

Gnomad OTH exome AF: 0.00463

GnomAD4 exome AF: 0.00647 AC: 9269 AN: 1432916 Hom.: 28 Cov.: 35 AF XY: 0.00630 AC XY: 4476 AN XY: 710138

Gnomad4 AFR exome AF: 0.000851

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.000274

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000470

Gnomad4 FIN exome AF: 0.00746

Gnomad4 NFE exome AF: 0.00759

Gnomad4 OTH exome AF: 0.00688

GnomAD4 genome AF: 0.00458 AC: 698 AN: 152300 Hom.: 1 Cov.: 31 AF XY: 0.00426 AC XY: 317 AN XY: 74468

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00650

Gnomad4 NFE AF: 0.00747

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00595 Hom.: 7

Bravo AF: 0.00397

TwinsUK AF: 0.00566 AC: 21

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00651 AC: 56

ExAC AF: 0.00330 AC: 399

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	ANKRD2: BP4 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.23	T;.;.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D;D;D;D
MetaRNN	Benign	0.0077	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.0	L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.5	D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Uncertain	0.018	D;D;D;D
Polyphen		0.91	P;D;.;.
Vest4		0.28
MVP		0.81
MPC		0.55
ClinPred		0.038	T
GERP RS		5.5
Varity_R		0.32
gMVP		0.55

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: rs36020819; hg19: chr10-99338262;