dbSNP rs2920781: CATSPER2:c.1397-121C>T (chr15-43632484-G-A) – ACMG Classification: Benign (-20 pts)

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.1397-121C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,430,064 control chromosomes in the GnomAD database, including 19,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 5820 hom., cov: 32)

Exomes 𝑓: 0.12 ( 13341 hom. )

Consequence

CATSPER2
NM_172095.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0860

Publications

8 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-43632484-G-A is Benign according to our data. Variant chr15-43632484-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPER2	NM_172095.4 link	c.1397-121C>T		intron_variant	Intron 11 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.1397-121C>T		intron_variant	Intron 11 of 12	2	NM_172095.4	ENSP00000380088.3		Q96P56-1
ENSG00000284772	ENST00000643290.1 link	n.-201C>T		upstream_gene_variant				ENSP00000495476.1		A0A2R8Y6Q2

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32852

AN:

151590

Hom.:

5804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.0405

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.0935

Gnomad OTH

AF:

0.190

GnomAD4 exome

AF:

0.118

AC:

150992

AN:

1278356

Hom.:

13341

Cov.:

AF XY:

0.119

AC XY:

76116

AN XY:

640974

show subpopulations

African (AFR)

AF:

0.497

AC:

14427

AN:

29052

American (AMR)

AF:

0.198

AC:

7716

AN:

39060

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

4572

AN:

24720

East Asian (EAS)

AF:

0.269

AC:

10031

AN:

37256

South Asian (SAS)

AF:

0.174

AC:

13863

AN:

79664

European-Finnish (FIN)

AF:

0.0406

AC:

1777

AN:

43768

Middle Eastern (MID)

AF:

0.137

AC:

594

AN:

4332

European-Non Finnish (NFE)

AF:

0.0935

AC:

90301

AN:

966192

Other (OTH)

AF:

0.142

AC:

7711

AN:

54312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

6297

12594

18890

25187

31484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3478

6956

10434

13912

17390

<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:

0.217

AC:

32915

AN:

151708

Hom.:

5820

Cov.:

AF XY:

0.214

AC XY:

15867

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.476

AC:

19634

AN:

41280

American (AMR)

AF:

0.195

AC:

2969

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

623

AN:

3460

East Asian (EAS)

AF:

0.276

AC:

1428

AN:

5172

South Asian (SAS)

AF:

0.194

AC:

929

AN:

4782

European-Finnish (FIN)

AF:

0.0405

AC:

427

AN:

10554

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0935

AC:

6349

AN:

67914

Other (OTH)

AF:

0.194

AC:

408

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1023

2046

3069

4092

5115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.157

Hom.:

611

Bravo

AF:

0.244

Asia WGS

AF:

0.242

AC:

841

AN:

3478

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

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.4

(source)

DANN

Benign

0.77

PhyloP100

-0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over