chr15-43632936-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 4P and 16B. PVS1_StrongBP6_Very_StrongBA1

The NM_172095.4(CATSPER2):c.1179-2A>T variant causes a splice acceptor, intron 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, intron

Scores

Splicing: ADA: 0.9960

Clinical Significance

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

Conservation

PhyloP100: -0.541

Publications

12 publications found

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:

ENSG00000309475 (HGNC:):

ENSG00000309475 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.13684872 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 VariationId 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 rank	MANE	Protein	UniProt
CATSPER2	NM_172095.4 link	c.1179-2A>T		splice_acceptor_variant, intron_variant	Intron 10 of 12	ENST00000396879.8	NP_742093.1	Q96P56-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPER2	ENST00000396879.8 link	c.1179-2A>T		splice_acceptor_variant, intron_variant	Intron 10 of 12	2	NM_172095.4	ENSP00000380088.3		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

GnomAD2 exomes

AF:

0.317

AC:

77743

AN:

245106

AF XY:

0.314

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 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

African (AFR)

AF:

0.728

AC:

23444

AN:

32188

American (AMR)

AF:

0.305

AC:

13473

AN:

44228

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

9802

AN:

25840

East Asian (EAS)

AF:

0.332

AC:

13092

AN:

39448

South Asian (SAS)

AF:

0.364

AC:

30904

AN:

84892

European-Finnish (FIN)

AF:

0.181

AC:

9589

AN:

52880

Middle Eastern (MID)

AF:

0.392

AC:

2226

AN:

5672

European-Non Finnish (NFE)

AF:

0.271

AC:

293827

AN:

1083486

Other (OTH)

AF:

0.317

AC:

18772

AN:

59228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

12707

25413

38120

50826

63533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9950

19900

29850

39800

49750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.399

AC:

60181

AN:

150666

Hom.:

15171

Cov.:

AF XY:

0.394

AC XY:

28992

AN XY:

73630

show subpopulations

African (AFR)

AF:

0.711

AC:

28951

AN:

40734

American (AMR)

AF:

0.340

AC:

5161

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1283

AN:

3436

East Asian (EAS)

AF:

0.324

AC:

1665

AN:

5142

South Asian (SAS)

AF:

0.356

AC:

1696

AN:

4760

European-Finnish (FIN)

AF:

0.179

AC:

1875

AN:

10498

Middle Eastern (MID)

AF:

0.449

AC:

131

AN:

292

European-Non Finnish (NFE)

AF:

0.273

AC:

18430

AN:

67624

Other (OTH)

AF:

0.376

AC:

789

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1506

3011

4517

6022

7528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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% -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Rare genetic deafness

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-0.93

CADD

Benign

(source)

DANN

Benign

0.43

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.025

PhyloP100

-0.54

GERP RS

-2.8

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over