15-43632949-T-G

Variant names:

• chr15-43632949-T-G
• rs7169112
• NM_172095.4:c.1179-15A>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.1179-15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 150,616 control chromosomes in the GnomAD database, including 15,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.40 (15185 hom., cov: 30)
  • Exomes 𝑓: 0.29 (66670 hom.)
  • Failed GnomAD Quality Control
• Consequence: CATSPER2 NM_172095.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.798
• Publications: 9 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-43632949-T-G is Benign according to our data. Variant chr15-43632949-T-G is described in ClinVar as Benign. ClinVar VariationId is 1247397.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.1179-15A>C		intron	N/A	NP_742093.1	Q96P56-1
	CATSPER2	NM_001282310.2		c.1197-21A>C		intron	N/A	NP_001269239.1	F8W9H2
	CATSPER2	NM_001282309.3		c.1179-21A>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.1179-15A>C		intron	N/A	ENSP00000380088.3	Q96P56-1
	CATSPER2	ENST00000381761.6	TSL:1	c.1197-21A>C		intron	N/A	ENSP00000371180.1	F8W9H2
	CATSPER2	ENST00000433380.5	TSL:1	n.1179-586A>C		intron	N/A	ENSP00000389746.1	Q96P56-3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60099 AN: 150504 Hom.: 15140 Cov.: 30

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.376

GnomAD2 exomes AF: 0.318 AC: 76693 AN: 241396 AF XY: 0.314

Gnomad AFR exome AF: 0.712

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.329

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.304

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.290 AC: 412234 AN: 1420536 Hom.: 66670 Cov.: 27 AF XY: 0.292 AC XY: 206875 AN XY: 708330

African (AFR) AF: 0.727 AC: 23221 AN: 31922

American (AMR) AF: 0.305 AC: 13412 AN: 44042

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 9773 AN: 25782

East Asian (EAS) AF: 0.332 AC: 13079 AN: 39394

South Asian (SAS) AF: 0.364 AC: 30749 AN: 84522

European-Finnish (FIN) AF: 0.182 AC: 9512 AN: 52322

Middle Eastern (MID) AF: 0.393 AC: 2199 AN: 5602

European-Non Finnish (NFE) AF: 0.271 AC: 291664 AN: 1078038

Other (OTH) AF: 0.316 AC: 18625 AN: 58912

GnomAD4 genome AF: 0.400 AC: 60195 AN: 150616 Hom.: 15185 Cov.: 30 AF XY: 0.394 AC XY: 28999 AN XY: 73610

African (AFR) AF: 0.711 AC: 28980 AN: 40748

American (AMR) AF: 0.340 AC: 5150 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1281 AN: 3444

East Asian (EAS) AF: 0.325 AC: 1671 AN: 5140

South Asian (SAS) AF: 0.356 AC: 1690 AN: 4746

European-Finnish (FIN) AF: 0.179 AC: 1875 AN: 10486

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.273 AC: 18427 AN: 67594

Other (OTH) AF: 0.377 AC: 791 AN: 2098

Alfa AF: 0.343 Hom.: 1985

Bravo AF: 0.429

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	-0.92
CADD	Benign	7.3
DANN	Benign	0.24
PhyloP100		0.80
BranchPoint Hunter		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7169112; hg19: chr15-43925147; COSMIC: COSV58661474; COSMIC: COSV58661474;