15-43631976-C-T

Variant names:

• chr15-43631976-C-T
• rs28366727
• NM_172095.4:c.1561+223G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_172095.4(CATSPER2):​c.1561+223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 151,722 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0070 (33 hom., cov: 31)
• Consequence: CATSPER2 NM_172095.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPER2	NM_172095.4	c.1561+223G>A		intron_variant	Intron 12 of 12	ENST00000396879.8	NP_742093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPER2	ENST00000396879.8	c.1561+223G>A		intron_variant	Intron 12 of 12	2	NM_172095.4	ENSP00000380088.3
ENSG00000284772	ENST00000643290.1	n.85+223G>A		intron_variant	Intron 1 of 8			ENSP00000495476.1

Frequencies

GnomAD3 genomes AF: 0.00699 AC: 1060 AN: 151604 Hom.: 33 Cov.: 31

Gnomad AFR AF: 0.000704

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00555

Gnomad OTH AF: 0.00526

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

GnomAD4 genome AF: 0.00699 AC: 1060 AN: 151722 Hom.: 33 Cov.: 31 AF XY: 0.00885 AC XY: 656 AN XY: 74126

Gnomad4 AFR AF: 0.000702

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0562

Gnomad4 NFE AF: 0.00556

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.0103 Hom.: 247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28366727; hg19: chr15-43924174;