15-43635172-T-C

Variant names:

• chr15-43635172-T-C
• rs12898584
• NM_172095.4:c.1178+188A>G

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.1178+188A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 650,816 control chromosomes in the GnomAD database, including 8,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1673 hom., cov: 29)
  • Exomes 𝑓: 0.15 (6790 hom.)
• Consequence: CATSPER2 NM_172095.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.729
• Publications: 1 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=-0.87).
• BP6: Variant 15-43635172-T-C is Benign according to our data. Variant chr15-43635172-T-C is described in ClinVar as Benign. ClinVar VariationId is 1268473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 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.1178+188A>G		intron	N/A	NP_742093.1	Q96P56-1
	CATSPER2	NM_001282310.2		c.1196+188A>G		intron	N/A	NP_001269239.1	F8W9H2
	CATSPER2	NM_001282309.3		c.1178+188A>G		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.1178+188A>G		intron	N/A	ENSP00000380088.3	Q96P56-1
	CATSPER2	ENST00000381761.6	TSL:1	c.1196+188A>G		intron	N/A	ENSP00000371180.1	F8W9H2
	CATSPER2	ENST00000433380.5	TSL:1	n.1178+188A>G		intron	N/A	ENSP00000389746.1	Q96P56-3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 19901 AN: 149816 Hom.: 1672 Cov.: 29

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.147

GnomAD2 exomes AF: 0.126 AC: 16707 AN: 133014 AF XY: 0.130

Gnomad AFR exome AF: 0.0716

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.00294

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.148 AC: 73987 AN: 500884 Hom.: 6790 Cov.: 5 AF XY: 0.151 AC XY: 40448 AN XY: 268400

African (AFR) AF: 0.0773 AC: 1016 AN: 13136

American (AMR) AF: 0.104 AC: 2366 AN: 22804

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 2739 AN: 15142

East Asian (EAS) AF: 0.00123 AC: 40 AN: 32564

South Asian (SAS) AF: 0.176 AC: 9013 AN: 51114

European-Finnish (FIN) AF: 0.105 AC: 4948 AN: 46946

Middle Eastern (MID) AF: 0.230 AC: 822 AN: 3568

European-Non Finnish (NFE) AF: 0.170 AC: 48921 AN: 288518

Other (OTH) AF: 0.152 AC: 4122 AN: 27092

GnomAD4 genome AF: 0.133 AC: 19916 AN: 149932 Hom.: 1673 Cov.: 29 AF XY: 0.129 AC XY: 9475 AN XY: 73168

African (AFR) AF: 0.0814 AC: 3328 AN: 40862

American (AMR) AF: 0.128 AC: 1926 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 642 AN: 3436

East Asian (EAS) AF: 0.00137 AC: 7 AN: 5098

South Asian (SAS) AF: 0.151 AC: 709 AN: 4706

European-Finnish (FIN) AF: 0.101 AC: 1027 AN: 10160

Middle Eastern (MID) AF: 0.245 AC: 71 AN: 290

European-Non Finnish (NFE) AF: 0.175 AC: 11796 AN: 67330

Other (OTH) AF: 0.146 AC: 303 AN: 2082

Alfa AF: 0.135 Hom.: 240

Bravo AF: 0.131

ClinVar

ClinVar submissions

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	-0.87
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		0.73
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: rs12898584; hg19: chr15-43927370;