Genetic Variant CATSPER2:p.Gly480Arg (chr15-43632322-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_172095.4(CATSPER2):c.1438G>C(p.Gly480Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CATSPER2
NM_172095.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.1438G>C	p.Gly480Arg	missense	Exon 12 of 13	NP_742093.1	Q96P56-1
CATSPER2	NM_001282310.2		c.1450G>C	p.Gly484Arg	missense	Exon 12 of 13	NP_001269239.1	F8W9H2
CATSPER2	NM_001282309.3		c.1432G>C	p.Gly478Arg	missense	Exon 13 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.1438G>C	p.Gly480Arg	missense	Exon 12 of 13	ENSP00000380088.3	Q96P56-1
CATSPER2	ENST00000381761.6	TSL:1	c.1450G>C	p.Gly484Arg	missense	Exon 12 of 13	ENSP00000371180.1	F8W9H2
CATSPER2	ENST00000433380.5	TSL:1	n.1220G>C		non_coding_transcript_exon	Exon 10 of 11	ENSP00000389746.1	Q96P56-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111880

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.66

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.68

MetaSVM

Uncertain

0.63

MutationAssessor

Uncertain

2.6

PhyloP100

1.9

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.8

REVEL

Pathogenic

0.67

Sift

Benign

0.072

Sift4G

Uncertain

0.031

Polyphen

0.99

Vest4

0.41

MutPred

0.39

Gain of helix (P = 0.0425)

MVP

0.88

MPC

0.79

ClinPred

0.98

GERP RS

4.2

Varity_R

0.26

gMVP

0.27

Mutation Taster

=91/9

polymorphism

(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