15-43647444-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

40 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:

PPIP5K1P1-CATSPER2 (HGNC:):

PPIP5K1P1-CATSPER2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172095.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CATSPER2	NM_172095.4	MANE Select	c.169G>A	p.Val57Ile	missense	Exon 3 of 13	NP_742093.1
CATSPER2	NM_001282310.2		c.187G>A	p.Val63Ile	missense	Exon 3 of 13	NP_001269239.1
CATSPER2	NM_001282309.3		c.169G>A	p.Val57Ile	missense	Exon 4 of 14	NP_001269238.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CATSPER2	ENST00000396879.8	TSL:2 MANE Select	c.169G>A	p.Val57Ile	missense	Exon 3 of 13	ENSP00000380088.3
CATSPER2	ENST00000381761.6	TSL:1	c.187G>A	p.Val63Ile	missense	Exon 3 of 13	ENSP00000371180.1
CATSPER2	ENST00000415968.2	TSL:1	n.390G>A		non_coding_transcript_exon	Exon 3 of 5

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

GnomAD2 exomes

AF:

0.136

AC:

34265

AN:

251204

AF XY:

0.131

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 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

African (AFR)

AF:

0.259

AC:

8659

AN:

33442

American (AMR)

AF:

0.187

AC:

8346

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4803

AN:

26124

East Asian (EAS)

AF:

0.272

AC:

10811

AN:

39686

South Asian (SAS)

AF:

0.130

AC:

11237

AN:

86218

European-Finnish (FIN)

AF:

0.0404

AC:

2157

AN:

53410

Middle Eastern (MID)

AF:

0.120

AC:

688

AN:

5756

European-Non Finnish (NFE)

AF:

0.0964

AC:

107113

AN:

1111336

Other (OTH)

AF:

0.125

AC:

7552

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

7944

15888

23833

31777

39721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4204

8408

12612

16816

21020

<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:

0.148

AC:

22502

AN:

151672

Hom.:

2245

Cov.:

AF XY:

0.147

AC XY:

10887

AN XY:

74138

show subpopulations

African (AFR)

AF:

0.241

AC:

9945

AN:

41280

American (AMR)

AF:

0.170

AC:

2595

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

620

AN:

3462

East Asian (EAS)

AF:

0.277

AC:

1429

AN:

5150

South Asian (SAS)

AF:

0.142

AC:

681

AN:

4788

European-Finnish (FIN)

AF:

0.0403

AC:

425

AN:

10558

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0936

AC:

6350

AN:

67878

Other (OTH)

AF:

0.148

AC:

313

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

892

1784

2676

3568

4460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.120

Hom.:

6658

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

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.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.8

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.031

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.056

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

0.48

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.060

REVEL

Benign

0.072

Sift

Benign

0.097

Sift4G

Uncertain

0.035

Polyphen

0.0

Vest4

0.059

MPC

0.20

ClinPred

0.0020

GERP RS

2.2

Varity_R

0.027

gMVP

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over