15-43632894-A-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.1219T>A(p.Ser407Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,609,390 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S407P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.017 ( 99 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 90 hom. )

Consequence

CATSPER2
NM_172095.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.869

Publications

1 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=0.0031799674).

BP6

Variant 15-43632894-A-T is Benign according to our data. Variant chr15-43632894-A-T is described in ClinVar as Benign. ClinVar VariationId is 1277659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0575 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	UniProt
CATSPER2	NM_172095.4	MANE Select	c.1219T>A	p.Ser407Thr	missense	Exon 11 of 13	NP_742093.1	Q96P56-1
CATSPER2	NM_001282310.2		c.1231T>A	p.Ser411Thr	missense	Exon 11 of 13	NP_001269239.1	F8W9H2
CATSPER2	NM_001282309.3		c.1213T>A	p.Ser405Thr	missense	Exon 12 of 14	NP_001269238.1	Q96P56-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CATSPER2	ENST00000396879.8	TSL:2 MANE Select	c.1219T>A	p.Ser407Thr	missense	Exon 11 of 13	ENSP00000380088.3	Q96P56-1
CATSPER2	ENST00000381761.6	TSL:1	c.1231T>A	p.Ser411Thr	missense	Exon 11 of 13	ENSP00000371180.1	F8W9H2
CATSPER2	ENST00000433380.5	TSL:1	n.1179-531T>A		intron	N/A	ENSP00000389746.1	Q96P56-3

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2564

AN:

151726

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0596

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00486

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00412

AC:

1031

AN:

250332

AF XY:

0.00297

show subpopulations

Gnomad AFR exome

AF:

0.0596

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00163

AC:

2376

AN:

1457546

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

987

AN XY:

725360

show subpopulations

African (AFR)

AF:

0.0611

AC:

2038

AN:

33380

American (AMR)

AF:

0.00226

AC:

101

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1108276

Other (OTH)

AF:

0.00352

AC:

212

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

115

231

346

462

577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.0169

AC:

2566

AN:

151844

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1198

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.0595

AC:

2460

AN:

41368

American (AMR)

AF:

0.00479

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000209

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67924

Other (OTH)

AF:

0.0114

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

116

233

349

466

582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00108

Hom.:

Bravo

AF:

0.0197

ESP6500AA

AF:

0.0551

AC:

242

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00523

AC:

635

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.037

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.041

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.34

PhyloP100

-0.87

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.60

REVEL

Benign

0.16

Sift

Benign

0.58

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.078

MVP

0.40

MPC

0.20

ClinPred

0.0041

GERP RS

-6.1

Varity_R

0.051

gMVP

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over