NM_182758.4:c.*3114A>G

Variant names:

• chr15-53514585-T-C
• rs72745122
• NM_182758.4:c.*3114A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182758.4(WDR72):​c.*3114A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.091 in 152,170 control chromosomes in the GnomAD database, including 720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (720 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: WDR72 NM_182758.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.499
• Publications: 2 publications found

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]

WDR72 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• amelogenesis imperfecta hypomaturation type 2A3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal tubular acidosis

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000287596 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-53514585-T-C is Benign according to our data. Variant chr15-53514585-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 316499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182758.4. 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
	WDR72	NM_182758.4	MANE Select	c.*3114A>G		3_prime_UTR	Exon 20 of 20	NP_877435.3	Q3MJ13
	WDR72	NM_001277176.2		c.*3114A>G		3_prime_UTR	Exon 3 of 3	NP_001264105.1	A0A087WTC3
	WDR72	NR_102334.2		n.6663A>G		non_coding_transcript_exon	Exon 20 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR72	ENST00000360509.10	TSL:1 MANE Select	c.*3114A>G		3_prime_UTR	Exon 20 of 20	ENSP00000353699.5	Q3MJ13
	WDR72	ENST00000396328.5	TSL:1	c.*3114A>G		3_prime_UTR	Exon 20 of 20	ENSP00000379619.1	Q3MJ13
	WDR72	ENST00000567224.1	TSL:1	n.3489A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13851 AN: 152056 Hom.: 719 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.0664

Gnomad EAS AF: 0.0873

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0865

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0910 AC: 13846 AN: 152170 Hom.: 720 Cov.: 32 AF XY: 0.0915 AC XY: 6809 AN XY: 74398

African (AFR) AF: 0.0461 AC: 1915 AN: 41540

American (AMR) AF: 0.0997 AC: 1523 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0664 AC: 230 AN: 3462

East Asian (EAS) AF: 0.0871 AC: 450 AN: 5168

South Asian (SAS) AF: 0.0962 AC: 464 AN: 4822

European-Finnish (FIN) AF: 0.124 AC: 1313 AN: 10596

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.113 AC: 7685 AN: 67990

Other (OTH) AF: 0.0870 AC: 184 AN: 2114

Alfa AF: 0.0880 Hom.: 235

Bravo AF: 0.0868

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Amelogenesis Imperfecta, Recessive (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

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: rs72745122; hg19: chr15-53806782;