15-43632942-A-G

Variant names:

• chr15-43632942-A-G
• rs7167634
• NM_172095.4:c.1179-8T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172095.4(CATSPER2):​c.1179-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 150,662 control chromosomes in the GnomAD database, including 15,163 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (15163 hom., cov: 29)
  • Exomes 𝑓: 0.29 (67559 hom.)
  • Failed GnomAD Quality Control
• Consequence: CATSPER2 NM_172095.4 splice_region, intron
• Scores: Splicing: ADA: 0.00006217
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.12

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]

PPIP5K1P1-CATSPER2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 15-43632942-A-G is Benign according to our data. Variant chr15-43632942-A-G is described in ClinVar as [Benign]. Clinvar id is 517821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPER2	NM_172095.4	c.1179-8T>C		splice_region_variant, intron_variant	Intron 10 of 12	ENST00000396879.8	NP_742093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPER2	ENST00000396879.8	c.1179-8T>C		splice_region_variant, intron_variant	Intron 10 of 12	2	NM_172095.4	ENSP00000380088.3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60067 AN: 150550 Hom.: 15118 Cov.: 29

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.377

GnomAD3 exomes AF: 0.317 AC: 77262 AN: 243608 Hom.: 13822 AF XY: 0.314 AC XY: 41553 AN XY: 132514

Gnomad AFR exome AF: 0.713

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.329

Gnomad SAS exome AF: 0.362

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.304

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.291 AC: 415865 AN: 1428744 Hom.: 67559 Cov.: 28 AF XY: 0.293 AC XY: 208533 AN XY: 712108

Gnomad4 AFR exome AF: 0.729

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.364

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.399 AC: 60163 AN: 150662 Hom.: 15163 Cov.: 29 AF XY: 0.394 AC XY: 28979 AN XY: 73628

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.378

Alfa AF: 0.333 Hom.: 1804

Bravo AF: 0.429

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.31
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000062
dbscSNV1_RF	Benign	0.030
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs7167634; hg19: chr15-43925140;