15-43630388-T-C

Variant names:

• chr15-43630388-T-C
• rs2915776
• NM_172095.4:c.*313A>G

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.*313A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 409,544 control chromosomes in the GnomAD database, including 9,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (5540 hom., cov: 31)
  • Exomes 𝑓: 0.13 (3529 hom.)
• Consequence: CATSPER2 NM_172095.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.302

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]

ENSG00000284772 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 15-43630388-T-C is Benign according to our data. Variant chr15-43630388-T-C is described in ClinVar as [Benign]. Clinvar id is 1290268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPER2	NM_172095.4	c.*313A>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000396879.8	NP_742093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPER2	ENST00000396879	c.*313A>G		3_prime_UTR_variant	Exon 13 of 13	2	NM_172095.4	ENSP00000380088.3
ENSG00000284772	ENST00000643290.1	n.85+1811A>G		intron_variant	Intron 1 of 8			ENSP00000495476.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32218 AN: 151560 Hom.: 5524 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.134 AC: 34655 AN: 257866 Hom.: 3529 Cov.: 3 AF XY: 0.137 AC XY: 19327 AN XY: 140914

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.0410

Gnomad4 NFE exome AF: 0.0939

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.213 AC: 32280 AN: 151678 Hom.: 5540 Cov.: 31 AF XY: 0.210 AC XY: 15547 AN XY: 74132

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.0398

Gnomad4 NFE AF: 0.0935

Gnomad4 OTH AF: 0.190

Alfa AF: 0.163 Hom.: 473

Bravo AF: 0.239

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.93
CADD	Benign	2.5
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2915776; hg19: chr15-43922586;