15-43647444-C-T

Position:

chr15-43647444-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_172095.4(CATSPER2):c.169G>A(p.Val57Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,612,710 control chromosomes in the GnomAD database, including 14,243 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2245 hom., cov: 32)

Exomes 𝑓: 0.11 ( 11998 hom. )

Consequence

CATSPER2
NM_172095.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.477

Variant links:

Genes affected

CATSPER2 (HGNC:18810): (cation channel sperm associated 2) This gene encodes a member of a family of cation channel proteins that localize to the flagellum of spermatozoa. Defects at this locus causes male infertility. Alternatively spliced transcript variants have been observed at this locus. Readthrough transcription originates upstream of this locus in diphosphoinositol pentakisphosphate kinase 1 pseudogene 1 and is represented by GeneID:110006325. Related pseudogenes are found next to this locus on chromosome 15 and on chromosome 5. [provided by RefSeq, Mar 2017]

CATSPER2 links:

PPIP5K1P1-CATSPER2 (HGNC:):

PPIP5K1P1-CATSPER2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005768895).

BP6

Variant 15-43647444-C-T is Benign according to our data. Variant chr15-43647444-C-T is described in ClinVar as [Benign]. Clinvar id is 508570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPER2	NM_172095.4 linkuse as main transcript	c.169G>A	p.Val57Ile	missense_variant	3/13	ENST00000396879.8	NP_742093.1
PPIP5K1P1-CATSPER2	NR_146339.1 linkuse as main transcript	n.3819G>A		non_coding_transcript_exon_variant	31/40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPER2	ENST00000396879.8 linkuse as main transcript	c.169G>A	p.Val57Ile	missense_variant	3/13	2	NM_172095.4	ENSP00000380088	P4	Q96P56-1

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22467

AN:

151554

Hom.:

2239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0936

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.136

AC:

34265

AN:

251204

Hom.:

3247

AF XY:

0.131

AC XY:

17799

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.238

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.0388

Gnomad NFE exome

AF:

0.0967

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.110

AC:

161366

AN:

1461038

Hom.:

11998

Cov.:

AF XY:

0.110

AC XY:

80248

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.272

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.0404

Gnomad4 NFE exome

AF:

0.0964

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.148

AC:

22502

AN:

151672

Hom.:

2245

Cov.:

AF XY:

0.147

AC XY:

10887

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.241

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.0403

Gnomad4 NFE

AF:

0.0936

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.118

Hom.:

3451

Bravo

AF:

0.166

TwinsUK

AF:

0.0936

AC:

347

ALSPAC

AF:

0.102

AC:

394

ESP6500AA

AF:

0.232

AC:

1019

ESP6500EA

AF:

0.0980

AC:

842

ExAC

AF:

0.135

AC:

16411

Asia WGS

AF:

0.206

AC:

718

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.8

DANN

Benign

0.94

DEOGEN2

Benign

0.031

T;.;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.056

T;T;T;T;T

MetaRNN

Benign

0.0058

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.;N;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.060

N;N;N;N;N

REVEL

Benign

0.072

Sift

Benign

0.097

T;T;T;T;T

Sift4G

Uncertain

0.035

D;D;D;.;.

Polyphen

0.0

B;B;.;.;.

Vest4

0.059

MPC

0.20

ClinPred

0.0020

GERP RS

2.2

Varity_R

0.027

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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