15-43631976-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_172095.4(CATSPER2):​c.1561+223G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,658 control chromosomes in the GnomAD database, including 14,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (14117 hom., cov: 31)
• Consequence: CATSPER2 NM_172095.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-43631976-C-G is Benign according to our data. Variant chr15-43631976-C-G is described in ClinVar as [Benign]. Clinvar id is 1287819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58116 AN: 151540 Hom.: 14069 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.384 AC: 58215 AN: 151658 Hom.: 14117 Cov.: 31 AF XY: 0.377 AC XY: 27912 AN XY: 74092

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.360

Alfa AF: 0.139 Hom.: 247

Bravo AF: 0.413

Asia WGS AF: 0.323 AC: 1128 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs28366727; hg19: chr15-43924174;