rs7169097

Variant names:

• chr15-43632936-T-A
• rs7169097
• NM_172095.4:c.1179-2A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-43632936-T-A
• chr15-43632936-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 4P and 16B. PVS1_Strong BP6_Very_Strong BA1

The NM_172095.4(CATSPER2):​c.1179-2A>T variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 150,666 control chromosomes in the GnomAD database, including 15,171 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (15171 hom., cov: 30)
  • Exomes 𝑓: 0.29 (67378 hom.)
  • Failed GnomAD Quality Control
• Consequence: CATSPER2 NM_172095.4 splice_acceptor, intron
• Scores: Splicing: ADA: 0.9960
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.541
• Publications: 12 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 -12 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.13684872 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.2, offset of 6, new splice context is: atttcttctttatgttcaAGagg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BP6: Variant 15-43632936-T-A is Benign according to our data. Variant chr15-43632936-T-A is described in ClinVar as Benign. ClinVar VariationId is 402497.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.1179-2A>T		splice_acceptor intron	N/A	NP_742093.1	Q96P56-1
	CATSPER2	NM_001282310.2		c.1197-8A>T		splice_region intron	N/A	NP_001269239.1	F8W9H2
	CATSPER2	NM_001282309.3		c.1179-8A>T		splice_region 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.1179-2A>T		splice_acceptor intron	N/A	ENSP00000380088.3	Q96P56-1
	CATSPER2	ENST00000381761.6	TSL:1	c.1197-8A>T		splice_region intron	N/A	ENSP00000371180.1	F8W9H2
	CATSPER2	ENST00000433380.5	TSL:1	n.1179-573A>T		intron	N/A	ENSP00000389746.1	Q96P56-3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60087 AN: 150556 Hom.: 15127 Cov.: 30

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.317 AC: 77743 AN: 245106 AF XY: 0.314

Gnomad AFR exome AF: 0.713

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.382

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: 415129 AN: 1427862 Hom.: 67378 Cov.: 28 AF XY: 0.293 AC XY: 208243 AN XY: 711766

African (AFR) AF: 0.728 AC: 23444 AN: 32188

American (AMR) AF: 0.305 AC: 13473 AN: 44228

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 9802 AN: 25840

East Asian (EAS) AF: 0.332 AC: 13092 AN: 39448

South Asian (SAS) AF: 0.364 AC: 30904 AN: 84892

European-Finnish (FIN) AF: 0.181 AC: 9589 AN: 52880

Middle Eastern (MID) AF: 0.392 AC: 2226 AN: 5672

European-Non Finnish (NFE) AF: 0.271 AC: 293827 AN: 1083486

Other (OTH) AF: 0.317 AC: 18772 AN: 59228

GnomAD4 genome AF: 0.399 AC: 60181 AN: 150666 Hom.: 15171 Cov.: 30 AF XY: 0.394 AC XY: 28992 AN XY: 73630

African (AFR) AF: 0.711 AC: 28951 AN: 40734

American (AMR) AF: 0.340 AC: 5161 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1283 AN: 3436

East Asian (EAS) AF: 0.324 AC: 1665 AN: 5142

South Asian (SAS) AF: 0.356 AC: 1696 AN: 4760

European-Finnish (FIN) AF: 0.179 AC: 1875 AN: 10498

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

European-Non Finnish (NFE) AF: 0.273 AC: 18430 AN: 67624

Other (OTH) AF: 0.376 AC: 789 AN: 2096

Alfa AF: 0.349 Hom.: 1868

Bravo AF: 0.429

ExAC AF: 0.322 AC: 38937

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)
-	-	1	Rare genetic deafness (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.90	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	13
DANN	Benign	0.43
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.025	N
PhyloP100		-0.54
GERP RS		-2.8
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Benign	0.34
SpliceAI score (max)		0.65		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.65		Position offset: -8
DS_AL_spliceai		0.59		Position offset: -2

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

Other links and lift over

dbSNP: rs7169097; hg19: chr15-43925134; COSMIC: COSV58661467; COSMIC: COSV58661467;