Genetic Variant NM_172095.4:c.1219T>A (chr15-43632894-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPER2	NM_172095.4 link	c.1219T>A	p.Ser407Thr	missense_variant	Exon 11 of 13	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.1219T>A	p.Ser407Thr	missense_variant	Exon 11 of 13	2	NM_172095.4	ENSP00000380088.3		Q96P56-1

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

GnomAD3 exomes

AF:

0.00412

AC:

1031

AN:

250332

Hom.:

AF XY:

0.00297

AC XY:

402

AN XY:

135432

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 SAS 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

Gnomad4 AFR exome

AF:

0.0611

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00352

GnomAD4 genome

AF:

0.0169

AC:

2566

AN:

151844

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1198

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.0595

Gnomad4 AMR

AF:

0.00479

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0114

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.037

DANN

Benign

0.33

DEOGEN2

Benign

0.041

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.37

T;T;T

MetaRNN

Benign

0.0032

T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.34

N;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.60

.;N;.

REVEL

Benign

0.16

Sift

Benign

0.58

.;T;.

Sift4G

Benign

0.39

.;T;.

Polyphen

0.0

B;B;.

Vest4

0.078

MVP

0.40

MPC

0.20

ClinPred

0.0041

GERP RS

-6.1

Varity_R

0.051

gMVP

0.10

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

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