rs551225

Positions:

• chr15-53710894-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000360509.10(WDR72):​c.917C>T​(p.Pro306Leu) variant causes a missense change. The variant allele was found at a frequency of 0.456 in 1,611,968 control chromosomes in the GnomAD database, including 173,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12394 hom., cov: 33)
  • Exomes 𝑓: 0.46 (161163 hom.)
• Consequence: WDR72 ENST00000360509.10 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 6.45

Genes affected

WDR72 (HGNC:26790): (WD repeat domain 72) This gene encodes a protein with eight WD-40 repeats. Mutations in this gene have been associated with amelogenesis imperfecta hypomaturation type 2A3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017650723).
• BP6: Variant 15-53710894-G-A is Benign according to our data. Variant chr15-53710894-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 263003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-53710894-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR72	NM_182758.4	c.917C>T	p.Pro306Leu	missense_variant	9/20	ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.917C>T	p.Pro306Leu	missense_variant	9/20	1	NM_182758.4	ENSP00000353699	P4

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57869 AN: 151968 Hom.: 12400 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.425

GnomAD3 exomes AF: 0.410 AC: 102877 AN: 251010 Hom.: 22898 AF XY: 0.424 AC XY: 57477 AN XY: 135674

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.615

Gnomad EAS exome AF: 0.193

Gnomad SAS exome AF: 0.469

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.484

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.464 AC: 676833 AN: 1459882 Hom.: 161163 Cov.: 38 AF XY: 0.465 AC XY: 338080 AN XY: 726388

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.614

Gnomad4 EAS exome AF: 0.253

Gnomad4 SAS exome AF: 0.463

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.487

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.380 AC: 57855 AN: 152086 Hom.: 12394 Cov.: 33 AF XY: 0.373 AC XY: 27757 AN XY: 74354

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.421

Alfa AF: 0.467 Hom.: 23487

Bravo AF: 0.373

TwinsUK AF: 0.486 AC: 1801

ALSPAC AF: 0.486 AC: 1873

ESP6500AA AF: 0.216 AC: 949

ESP6500EA AF: 0.501 AC: 4304

ExAC AF: 0.411 AC: 49909

Asia WGS AF: 0.307 AC: 1067 AN: 3478

EpiCase AF: 0.508

EpiControl AF: 0.505

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 30476138) -

Amelogenesis imperfecta hypomaturation type 2A3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Amelogenesis Imperfecta, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;T;.;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	.;D;D;D;D
MetaRNN	Benign	0.0018	T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M;.;M;.;.
MutationTaster	Benign	1.3e-8	P;P;P;P
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.1	D;D;D;D;D
REVEL	Benign	0.29
Sift	Uncertain	0.012	D;T;D;T;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;.;D;.;.
Vest4		0.67
MPC		0.088
ClinPred		0.014	T
GERP RS		5.6
Varity_R		0.42
gMVP		0.65

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: rs551225; hg19: chr15-54003091; COSMIC: COSV64741305;