chr15-43647444-C-T

Variant names:

• chr15-43647444-C-T
• rs8042868
• NM_172095.4:c.169G>A

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.169G>A​(p.Val57Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,612,710 control chromosomes in the GnomAD database, including 14,243 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2245 hom., cov: 32)
  • Exomes 𝑓: 0.11 (11998 hom.)
• Consequence: CATSPER2 NM_172095.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.477
• Publications: 40 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]

PPIP5K1P1-CATSPER2 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.005768895).
• BP6: Variant 15-43647444-C-T is Benign according to our data. Variant chr15-43647444-C-T is described in ClinVar as Benign. ClinVar VariationId is 508570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 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.169G>A	p.Val57Ile	missense	Exon 3 of 13	NP_742093.1	Q96P56-1
	CATSPER2	NM_001282310.2		c.187G>A	p.Val63Ile	missense	Exon 3 of 13	NP_001269239.1	F8W9H2
	CATSPER2	NM_001282309.3		c.169G>A	p.Val57Ile	missense	Exon 4 of 14	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.169G>A	p.Val57Ile	missense	Exon 3 of 13	ENSP00000380088.3	Q96P56-1
	CATSPER2	ENST00000381761.6	TSL:1	c.187G>A	p.Val63Ile	missense	Exon 3 of 13	ENSP00000371180.1	F8W9H2
	CATSPER2	ENST00000415968.2	TSL:1	n.390G>A		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22467 AN: 151554 Hom.: 2239 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.144

GnomAD2 exomes AF: 0.136 AC: 34265 AN: 251204 AF XY: 0.131

Gnomad AFR exome AF: 0.238

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.287

Gnomad FIN exome AF: 0.0388

Gnomad NFE exome AF: 0.0967

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.110 AC: 161366 AN: 1461038 Hom.: 11998 Cov.: 33 AF XY: 0.110 AC XY: 80248 AN XY: 726866

African (AFR) AF: 0.259 AC: 8659 AN: 33442

American (AMR) AF: 0.187 AC: 8346 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4803 AN: 26124

East Asian (EAS) AF: 0.272 AC: 10811 AN: 39686

South Asian (SAS) AF: 0.130 AC: 11237 AN: 86218

European-Finnish (FIN) AF: 0.0404 AC: 2157 AN: 53410

Middle Eastern (MID) AF: 0.120 AC: 688 AN: 5756

European-Non Finnish (NFE) AF: 0.0964 AC: 107113 AN: 1111336

Other (OTH) AF: 0.125 AC: 7552 AN: 60352

GnomAD4 genome AF: 0.148 AC: 22502 AN: 151672 Hom.: 2245 Cov.: 32 AF XY: 0.147 AC XY: 10887 AN XY: 74138

African (AFR) AF: 0.241 AC: 9945 AN: 41280

American (AMR) AF: 0.170 AC: 2595 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3462

East Asian (EAS) AF: 0.277 AC: 1429 AN: 5150

South Asian (SAS) AF: 0.142 AC: 681 AN: 4788

European-Finnish (FIN) AF: 0.0403 AC: 425 AN: 10558

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0936 AC: 6350 AN: 67878

Other (OTH) AF: 0.148 AC: 313 AN: 2112

Alfa AF: 0.120 Hom.: 6658

Bravo AF: 0.166

TwinsUK AF: 0.0936 AC: 347

ALSPAC AF: 0.102 AC: 394

ESP6500AA AF: 0.232 AC: 1019

ESP6500EA AF: 0.0980 AC: 842

ExAC AF: 0.135 AC: 16411

Asia WGS AF: 0.206 AC: 718 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.8
DANN	Benign	0.94
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.056	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.48
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.072
Sift	Benign	0.097	T
Sift4G	Uncertain	0.035	D
Polyphen		0.0	B
Vest4		0.059
MPC		0.20
ClinPred		0.0020	T
GERP RS		2.2
Varity_R		0.027
gMVP		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs8042868; hg19: chr15-43939642; COSMIC: COSV58661716; COSMIC: COSV58661716;