chr15-53514185-C-T

Variant names:

• chr15-53514185-C-T
• rs185236656
• NM_182758.4:c.*3514G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_182758.4(WDR72):​c.*3514G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 152,224 control chromosomes in the GnomAD database, including 1 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 0.0015 (1 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: WDR72 NM_182758.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00149 (227/152224) while in subpopulation AFR AF= 0.0051 (212/41532). AF 95% confidence interval is 0.00454. There are 1 homozygotes in gnomad4. There are 99 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4	c.*3514G>A		3_prime_UTR_variant	Exon 20 of 20	ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509	c.*3514G>A		3_prime_UTR_variant	Exon 20 of 20	1	NM_182758.4	ENSP00000353699.5
WDR72	ENST00000396328	c.*3514G>A		3_prime_UTR_variant	Exon 20 of 20	1		ENSP00000379619.1
WDR72	ENST00000567224.1	n.3889G>A		non_coding_transcript_exon_variant	Exon 3 of 3	1
WDR72	ENST00000614174	c.*3514G>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000477754.1

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 227 AN: 152106 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00192

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

GnomAD4 genome AF: 0.00149 AC: 227 AN: 152224 Hom.: 1 Cov.: 32 AF XY: 0.00133 AC XY: 99 AN XY: 74436

Gnomad4 AFR AF: 0.00510

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00190

Bravo AF: 0.00180

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.60

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: rs185236656; hg19: chr15-53806382;