NM_001270454.2:c.110G>A

Variant names:

• chr16-69798721-G-A
• rs143303340
• NM_001270454.2:c.110G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001270454.2(WWP2):​c.110G>A​(p.Arg37Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: WWP2 NM_001270454.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.74

Genes affected

WWP2 (HGNC:16804): (WW domain containing E3 ubiquitin protein ligase 2) This gene encodes a member of the Nedd4 family of E3 ligases, which play an important role in protein ubiquitination. The encoded protein contains four WW domains and may play a role in multiple processes including chondrogenesis and the regulation of oncogenic signaling pathways via interactions with Smad proteins and the tumor suppressor PTEN. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 10. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWP2	NM_001270454.2	c.110G>A	p.Arg37Gln	missense_variant	Exon 3 of 24	ENST00000359154.7	NP_001257383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWP2	ENST00000359154.7	c.110G>A	p.Arg37Gln	missense_variant	Exon 3 of 24	1	NM_001270454.2	ENSP00000352069.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251294 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135798

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461822 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.073	T;T;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.60	D;D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.7	L;.;.;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.88	N;N;D;N
REVEL	Benign	0.28
Sift	Benign	0.46	T;T;D;T
Sift4G	Benign	0.54	T;D;D;D
Polyphen		0.99	D;.;.;.
Vest4		0.78
MutPred		0.57		Loss of MoRF binding (P = 0.0198);Loss of MoRF binding (P = 0.0198);Loss of MoRF binding (P = 0.0198);Loss of MoRF binding (P = 0.0198);
MVP		0.44
MPC		1.2
ClinPred		0.68	D
GERP RS		5.8
Varity_R		0.43
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs143303340; hg19: chr16-69832624; COSMIC: COSV100598557; COSMIC: COSV100598557;