XR_007064643.1:n.167-376C>G

Variant names:

• chr15-53513628-C-G
• rs7168365
• XR_007064643.1:n.167-376C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The XR_007064643.1(LOC105370826):​n.167-376C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: LOC105370826 XR_007064643.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 10 publications found

Genes affected

LOC105370826 (HGNC:):

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360509.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR72	NM_182758.4	MANE Select	c.*4071G>C		downstream_gene	N/A	NP_877435.3
	WDR72	NM_001277176.2		c.*4071G>C		downstream_gene	N/A	NP_001264105.1
	WDR72	NR_102334.2		n.*113G>C		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR72	ENST00000360509.10	TSL:1 MANE Select	c.*4071G>C		downstream_gene	N/A	ENSP00000353699.5
	WDR72	ENST00000396328.5	TSL:1	c.*4071G>C		downstream_gene	N/A	ENSP00000379619.1
	WDR72	ENST00000567224.1	TSL:1	n.*113G>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.085

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7168365; hg19: chr15-53805825;