rs1621807

Variant names:

• chr15-53655665-A-G
• rs1621807
• NM_182758.4:c.1962+9907T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182758.4(WDR72):​c.1962+9907T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0733 in 152,114 control chromosomes in the GnomAD database, including 1,006 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.073 (1006 hom., cov: 32)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4	c.1962+9907T>C		intron_variant	Intron 14 of 19	ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.1962+9907T>C		intron_variant	Intron 14 of 19	1	NM_182758.4	ENSP00000353699.5

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11131 AN: 151996 Hom.: 1003 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0694

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0521

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0733 AC: 11157 AN: 152114 Hom.: 1006 Cov.: 32 AF XY: 0.0734 AC XY: 5462 AN XY: 74382

African (AFR) AF: 0.214 AC: 8865 AN: 41480

American (AMR) AF: 0.0314 AC: 479 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.0692 AC: 357 AN: 5162

South Asian (SAS) AF: 0.0471 AC: 227 AN: 4816

European-Finnish (FIN) AF: 0.0198 AC: 210 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0131 AC: 893 AN: 68002

Other (OTH) AF: 0.0567 AC: 120 AN: 2116

Alfa AF: 0.0540 Hom.: 104

Bravo AF: 0.0792

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.47
PhyloP100		0.38
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: rs1621807; hg19: chr15-53947862;