chr15-43632484-G-A

Variant names:

• chr15-43632484-G-A
• rs2920781
• NM_172095.4:c.1397-121C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172095.4(CATSPER2):​c.1397-121C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,430,064 control chromosomes in the GnomAD database, including 19,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5820 hom., cov: 32)
  • Exomes 𝑓: 0.12 (13341 hom.)
• Consequence: CATSPER2 NM_172095.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0860
• Publications: 8 publications found

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]

ENSG00000309475 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-43632484-G-A is Benign according to our data. Variant chr15-43632484-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172095.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER2	NM_172095.4	MANE Select	c.1397-121C>T		intron	N/A	NP_742093.1
	CATSPER2	NM_001282310.2		c.1409-121C>T		intron	N/A	NP_001269239.1
	CATSPER2	NM_001282309.3		c.1391-121C>T		intron	N/A	NP_001269238.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER2	ENST00000396879.8	TSL:2 MANE Select	c.1397-121C>T		intron	N/A	ENSP00000380088.3
	CATSPER2	ENST00000381761.6	TSL:1	c.1409-121C>T		intron	N/A	ENSP00000371180.1
	CATSPER2	ENST00000433380.5	TSL:1	n.1179-121C>T		intron	N/A	ENSP00000389746.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32852 AN: 151590 Hom.: 5804 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.118 AC: 150992 AN: 1278356 Hom.: 13341 Cov.: 19 AF XY: 0.119 AC XY: 76116 AN XY: 640974

African (AFR) AF: 0.497 AC: 14427 AN: 29052

American (AMR) AF: 0.198 AC: 7716 AN: 39060

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4572 AN: 24720

East Asian (EAS) AF: 0.269 AC: 10031 AN: 37256

South Asian (SAS) AF: 0.174 AC: 13863 AN: 79664

European-Finnish (FIN) AF: 0.0406 AC: 1777 AN: 43768

Middle Eastern (MID) AF: 0.137 AC: 594 AN: 4332

European-Non Finnish (NFE) AF: 0.0935 AC: 90301 AN: 966192

Other (OTH) AF: 0.142 AC: 7711 AN: 54312

GnomAD4 genome AF: 0.217 AC: 32915 AN: 151708 Hom.: 5820 Cov.: 32 AF XY: 0.214 AC XY: 15867 AN XY: 74148

African (AFR) AF: 0.476 AC: 19634 AN: 41280

American (AMR) AF: 0.195 AC: 2969 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 623 AN: 3460

East Asian (EAS) AF: 0.276 AC: 1428 AN: 5172

South Asian (SAS) AF: 0.194 AC: 929 AN: 4782

European-Finnish (FIN) AF: 0.0405 AC: 427 AN: 10554

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0935 AC: 6349 AN: 67914

Other (OTH) AF: 0.194 AC: 408 AN: 2102

Alfa AF: 0.157 Hom.: 611

Bravo AF: 0.244

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.77
PhyloP100		-0.086
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2920781; hg19: chr15-43924682; COSMIC: COSV58661652; COSMIC: COSV58661652;