Genetic Variant CATSPER2:c.1561+223G>C (chr15-43631976-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_172095.4(CATSPER2):c.1561+223G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,658 control chromosomes in the GnomAD database, including 14,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 14117 hom., cov: 31)

Consequence

CATSPER2
NM_172095.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0950

Publications

6 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:

ENSG00000284772 (HGNC:):

ENSG00000284772 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-43631976-C-G is Benign according to our data. Variant chr15-43631976-C-G is described in ClinVar as Benign. ClinVar VariationId is 1287819.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 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	Effect	Exon Rank	Protein	UniProt
CATSPER2	NM_172095.4	MANE Select	c.1561+223G>C	intron	N/A	NP_742093.1	Q96P56-1
CATSPER2	NM_001282310.2		c.1573+223G>C	intron	N/A	NP_001269239.1	F8W9H2
CATSPER2	NM_001282309.3		c.1555+223G>C	intron	N/A	NP_001269238.1	Q96P56-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CATSPER2	ENST00000396879.8	TSL:2 MANE Select	c.1561+223G>C	intron	N/A	ENSP00000380088.3	Q96P56-1
CATSPER2	ENST00000381761.6	TSL:1	c.1573+223G>C	intron	N/A	ENSP00000371180.1	F8W9H2
CATSPER2	ENST00000433380.5	TSL:1	n.*98+223G>C	intron	N/A	ENSP00000389746.1	Q96P56-3

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58116

AN:

151540

Hom.:

14069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.674

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.358

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.384

AC:

58215

AN:

151658

Hom.:

14117

Cov.:

AF XY:

0.377

AC XY:

27912

AN XY:

74092

show subpopulations

African (AFR)

AF:

0.674

AC:

27859

AN:

41314

American (AMR)

AF:

0.334

AC:

5101

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1278

AN:

3460

East Asian (EAS)

AF:

0.278

AC:

1432

AN:

5154

South Asian (SAS)

AF:

0.348

AC:

1669

AN:

4792

European-Finnish (FIN)

AF:

0.145

AC:

1522

AN:

10530

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18266

AN:

67840

Other (OTH)

AF:

0.360

AC:

760

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1533

3066

4599

6132

7665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.139

Hom.:

247

Bravo

AF:

0.413

Asia WGS

AF:

0.323

AC:

1128

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.7

(source)

DANN

Benign

0.59

PhyloP100

0.095

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over