NM_001270454.2:c.574C>A

Variant names:

• chr16-69842119-C-A
• rs201287506
• NM_001270454.2:c.574C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001270454.2(WWP2):​c.574C>A​(p.Arg192Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R192R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WWP2 NM_001270454.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0003069
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP7: Synonymous conserved (PhyloP=1.75 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270454.2. 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
	WWP2	NM_001270454.2	MANE Select	c.574C>A	p.Arg192Arg	splice_region synonymous	Exon 6 of 24	NP_001257383.1	O00308-1
	WWP2	NM_007014.5		c.574C>A	p.Arg192Arg	splice_region synonymous	Exon 7 of 25	NP_008945.2
	WWP2	NM_001270453.2		c.226C>A	p.Arg76Arg	splice_region synonymous	Exon 3 of 21	NP_001257382.1	O00308-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWP2	ENST00000359154.7	TSL:1 MANE Select	c.574C>A	p.Arg192Arg	splice_region synonymous	Exon 6 of 24	ENSP00000352069.2	O00308-1
	WWP2	ENST00000903147.1		c.574C>A	p.Arg192Arg	splice_region synonymous	Exon 7 of 25	ENSP00000573206.1
	WWP2	ENST00000903148.1		c.574C>A	p.Arg192Arg	splice_region synonymous	Exon 7 of 25	ENSP00000573207.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459610 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725852

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 85848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111038

Other (OTH) AF: 0.0000166 AC: 1 AN: 60326

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.91
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.11
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: rs201287506; hg19: chr16-69876022;