rs7169097

Positions:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 4P and 16B. PVS1_StrongBP6_Very_StrongBA1

The NM_172095.4(CATSPER2):c.1179-2A>T variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 150,666 control chromosomes in the GnomAD database, including 15,171 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 15171 hom., cov: 30)

Exomes 𝑓: 0.29 ( 67378 hom. )

Failed GnomAD Quality Control

Consequence

CATSPER2
NM_172095.4 splice_acceptor

Scores

Splicing: ADA: 0.9960

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.541

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 -12 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.13622096 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.2, offset of 6, new splice context is: atttcttctttatgttcaAGagg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BP6

Variant 15-43632936-T-A is Benign according to our data. Variant chr15-43632936-T-A is described in ClinVar as [Benign]. Clinvar id is 402497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 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.1179-2A>T		splice_acceptor_variant		ENST00000396879.8	NP_742093.1
PPIP5K1P1-CATSPER2	NR_146339.1 linkuse as main transcript	n.4729-2A>T		splice_acceptor_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPER2	ENST00000396879.8 linkuse as main transcript	c.1179-2A>T		splice_acceptor_variant		2	NM_172095.4	ENSP00000380088	P4	Q96P56-1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60087

AN:

150556

Hom.:

15127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.436

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.375

GnomAD3 exomes

AF:

0.317

AC:

77743

AN:

245106

Hom.:

13953

AF XY:

0.314

AC XY:

41763

AN XY:

133184

show subpopulations

Gnomad AFR exome

AF:

0.713

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.382

Gnomad EAS exome

AF:

0.329

Gnomad SAS exome

AF:

0.362

Gnomad FIN exome

AF:

0.180

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.291

AC:

415129

AN:

1427862

Hom.:

67378

Cov.:

AF XY:

0.293

AC XY:

208243

AN XY:

711766

show subpopulations

Gnomad4 AFR exome

AF:

0.728

Gnomad4 AMR exome

AF:

0.305

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.332

Gnomad4 SAS exome

AF:

0.364

Gnomad4 FIN exome

AF:

0.181

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.317

GnomAD4 genome

AF:

0.399

AC:

60181

AN:

150666

Hom.:

15171

Cov.:

AF XY:

0.394

AC XY:

28992

AN XY:

73630

show subpopulations

Gnomad4 AFR

AF:

0.711

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.373

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.356

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.273

Gnomad4 OTH

AF:

0.376

Alfa

AF:

0.349

Hom.:

1868

Bravo

AF:

0.429

ExAC

AF:

0.322

AC:

38937

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 923/2178=42.4% -
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

- -

Rare genetic deafness

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-0.93

CADD

Benign

DANN

Benign

0.43

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.025

MutationTaster

Benign

1.0

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

GERP RS

-2.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Benign

0.34

SpliceAI score (max)

0.65

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.65

Position offset: -8

DS_AL_spliceai

0.59

Position offset: -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