15-43632936-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_172095.4(CATSPER2):​c.1179-2A>C variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Consequence

CATSPER2
NM_172095.4 splice_acceptor, intron

Scores

7
Splicing: ADA: 0.9942
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.541
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.13684872 fraction of the gene. Cryptic splice site detected, with MaxEntScore 4.1, offset of 6, new splice context is: atttcttctttacgttcaAGagg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CATSPER2NM_172095.4 linkc.1179-2A>C splice_acceptor_variant, intron_variant Intron 10 of 12 ENST00000396879.8 NP_742093.1 Q96P56-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CATSPER2ENST00000396879.8 linkc.1179-2A>C splice_acceptor_variant, intron_variant Intron 10 of 12 2 NM_172095.4 ENSP00000380088.3 Q96P56-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.93
CADD
Benign
15
DANN
Benign
0.47
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.028
N
GERP RS
-2.8

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.99
dbscSNV1_RF
Benign
0.34
SpliceAI score (max)
0.59
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.56
Position offset: -8
DS_AL_spliceai
0.59
Position offset: -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.

Other links and lift over

dbSNP: rs7169097; hg19: chr15-43925134; API