chr15-43632937-T-G

Variant names:

• chr15-43632937-T-G
• rs199882327
• NM_172095.4:c.1179-3A>C

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.1179-3A>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 150,672 control chromosomes in the GnomAD database, including 15,168 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 (15168 hom., cov: 30)
  • Exomes 𝑓: 0.29 (67450 hom.)
  • Failed GnomAD Quality Control
• Consequence: CATSPER2 NM_172095.4 splice_region, intron
• Scores: Splicing: ADA: 0.00004899
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.507
• Publications: 6 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=-0.99).
• BP6: Variant 15-43632937-T-G is Benign according to our data. Variant chr15-43632937-T-G is described in ClinVar as Benign. ClinVar VariationId is 517822.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.

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.1179-3A>C		splice_region intron	N/A	NP_742093.1	Q96P56-1
	CATSPER2	NM_001282310.2		c.1197-9A>C		intron	N/A	NP_001269239.1	F8W9H2
	CATSPER2	NM_001282309.3		c.1179-9A>C		intron	N/A	NP_001269238.1	Q96P56-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER2	ENST00000396879.8	TSL:2 MANE Select	c.1179-3A>C		splice_region intron	N/A	ENSP00000380088.3	Q96P56-1
	CATSPER2	ENST00000381761.6	TSL:1	c.1197-9A>C		intron	N/A	ENSP00000371180.1	F8W9H2
	CATSPER2	ENST00000433380.5	TSL:1	n.1179-574A>C		intron	N/A	ENSP00000389746.1	Q96P56-3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60079 AN: 150562 Hom.: 15124 Cov.: 30

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.317 AC: 77675 AN: 244874 AF XY: 0.314

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 FIN exome AF: 0.180

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.305

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.291 AC: 415379 AN: 1427870 Hom.: 67450 Cov.: 28 AF XY: 0.293 AC XY: 208345 AN XY: 711740

African (AFR) AF: 0.728 AC: 23451 AN: 32194

American (AMR) AF: 0.305 AC: 13476 AN: 44234

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 9803 AN: 25842

East Asian (EAS) AF: 0.332 AC: 13095 AN: 39444

South Asian (SAS) AF: 0.364 AC: 30911 AN: 84892

European-Finnish (FIN) AF: 0.181 AC: 9576 AN: 52840

Middle Eastern (MID) AF: 0.393 AC: 2232 AN: 5682

European-Non Finnish (NFE) AF: 0.271 AC: 294061 AN: 1083512

Other (OTH) AF: 0.317 AC: 18774 AN: 59230

GnomAD4 genome AF: 0.399 AC: 60173 AN: 150672 Hom.: 15168 Cov.: 30 AF XY: 0.394 AC XY: 28984 AN XY: 73626

African (AFR) AF: 0.711 AC: 28948 AN: 40732

American (AMR) AF: 0.340 AC: 5155 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1283 AN: 3442

East Asian (EAS) AF: 0.324 AC: 1668 AN: 5148

South Asian (SAS) AF: 0.356 AC: 1695 AN: 4764

European-Finnish (FIN) AF: 0.178 AC: 1874 AN: 10504

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.273 AC: 18430 AN: 67612

Other (OTH) AF: 0.376 AC: 789 AN: 2098

Alfa AF: 0.349 Hom.: 1868

Bravo AF: 0.429

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Rare genetic deafness (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.60
DANN	Benign	0.48
PhyloP100		-0.51
Mutation Taster		=78/22	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.020
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: rs199882327; hg19: chr15-43925135; COSMIC: COSV58661470; COSMIC: COSV58661470;