22-42019686-A-G

Variant names:

• chr22-42019686-A-G
• rs746353007
• NM_152613.3:c.196A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_152613.3(WBP2NL):​c.196A>G​(p.Ile66Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: WBP2NL NM_152613.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.326
• Publications: 0 publications found

Genes affected

WBP2NL (HGNC:28389): (WBP2 N-terminal like) WBP2NL is a sperm-specific WW domain-binding protein that promotes meiotic resumption and pronuclear development during oocyte fertilization (Wu et al., 2007 [PubMed 17289678]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03231582).
• BP6: Variant 22-42019686-A-G is Benign according to our data. Variant chr22-42019686-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2598365.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152613.3. 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
	WBP2NL	NM_152613.3	MANE Select	c.196A>G	p.Ile66Val	missense	Exon 3 of 6	NP_689826.2	Q6ICG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WBP2NL	ENST00000328823.13	TSL:1 MANE Select	c.196A>G	p.Ile66Val	missense	Exon 3 of 6	ENSP00000332983.9	Q6ICG8
	WBP2NL	ENST00000943073.1		c.196A>G	p.Ile66Val	missense	Exon 3 of 5	ENSP00000613132.1
	WBP2NL	ENST00000329620.9	TSL:2	n.196A>G		non_coding_transcript_exon	Exon 3 of 8	ENSP00000328800.5	Q6ICG8

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251436 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461872 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74362

African (AFR) AF: 0.0000965 AC: 4 AN: 41448

American (AMR) AF: 0.000458 AC: 7 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68046

Other (OTH) AF: 0.00144 AC: 3 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000117

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.048
DANN	Benign	0.27
DEOGEN2	Benign	0.097	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-1.7	N
PhyloP100		0.33
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.056
MutPred		0.29		Gain of catalytic residue at I66 (P = 0.0013)
MVP		0.20
MPC		0.16
ClinPred		0.038	T
GERP RS		-0.76
PromoterAI		0.015	Neutral
Varity_R		0.019
gMVP		0.15
Mutation Taster		=98/2	polymorphism

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: rs746353007; hg19: chr22-42415690;