15-53513957-C-G

Position:

• chr15-53513957-C-G

Variant summary

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

The NM_182758.4(WDR72):​c.*3742G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 152,244 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (179 hom., cov: 32)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: WDR72 NM_182758.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.381

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]

LOC105370826 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 15-53513957-C-G is Benign according to our data. Variant chr15-53513957-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 316486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR72	NM_182758.4	c.*3742G>C		3_prime_UTR_variant	20/20	ENST00000360509.10
LOC105370826	XR_007064645.1	n.167-47C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR72	ENST00000360509.10	c.*3742G>C		3_prime_UTR_variant	20/20	1	NM_182758.4	P4
WDR72	ENST00000396328.5	c.*3742G>C		3_prime_UTR_variant	20/20	1		P4
WDR72	ENST00000567224.1	n.4117G>C		non_coding_transcript_exon_variant	3/3	1
WDR72	ENST00000614174.4	c.*3742G>C		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6601 AN: 152098 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0589

Gnomad OTH AF: 0.0611

GnomAD4 exome AF: 0.107 AC: 3 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.136 AC XY: 3 AN XY: 22

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.0433 AC: 6598 AN: 152216 Hom.: 179 Cov.: 32 AF XY: 0.0410 AC XY: 3051 AN XY: 74390

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0507

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00329

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0416

Gnomad4 NFE AF: 0.0589

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0489 Hom.: 28

Bravo AF: 0.0432

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.59

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: rs79708164; hg19: chr15-53806154;