16-69798719-T-G

Variant names:

• chr16-69798719-T-G
• rs112425716
• NM_001270454.2:c.108T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001270454.2(WWP2):​c.108T>G​(p.Pro36Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,614,010 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (20 hom.)
• Consequence: WWP2 NM_001270454.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 16-69798719-T-G is Benign according to our data. Variant chr16-69798719-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3388039.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.68 with no splicing effect.
• BS2: High AC in GnomAd4 at 367 AD gene.

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.108T>G	p.Pro36Pro	synonymous	Exon 3 of 24	NP_001257383.1	O00308-1
	WWP2	NM_007014.5		c.108T>G	p.Pro36Pro	synonymous	Exon 4 of 25	NP_008945.2
	WWP2	NM_001270455.2		c.108T>G	p.Pro36Pro	synonymous	Exon 3 of 9	NP_001257384.1	O00308-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWP2	ENST00000359154.7	TSL:1 MANE Select	c.108T>G	p.Pro36Pro	synonymous	Exon 3 of 24	ENSP00000352069.2	O00308-1
	WWP2	ENST00000903147.1		c.108T>G	p.Pro36Pro	synonymous	Exon 4 of 25	ENSP00000573206.1
	WWP2	ENST00000903148.1		c.108T>G	p.Pro36Pro	synonymous	Exon 4 of 25	ENSP00000573207.1

Frequencies

GnomAD3 genomes AF: 0.00241 AC: 367 AN: 152056 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000556

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.00182 AC: 457 AN: 251304 AF XY: 0.00190

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00365

Gnomad NFE exome AF: 0.00303

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00266 AC: 3892 AN: 1461836 Hom.: 20 Cov.: 30 AF XY: 0.00272 AC XY: 1978 AN XY: 727222

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.000358 AC: 16 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00436 AC: 233 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00311 AC: 3453 AN: 1111988

Other (OTH) AF: 0.00258 AC: 156 AN: 60396

GnomAD4 genome AF: 0.00241 AC: 367 AN: 152174 Hom.: 1 Cov.: 32 AF XY: 0.00230 AC XY: 171 AN XY: 74392

African (AFR) AF: 0.000554 AC: 23 AN: 41514

American (AMR) AF: 0.000589 AC: 9 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00349 AC: 37 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00400 AC: 272 AN: 68004

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00326 Hom.: 0

Bravo AF: 0.00190

EpiCase AF: 0.00273

EpiControl AF: 0.00237

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.8
DANN	Benign	0.74
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs112425716; hg19: chr16-69832622;