5-111097388-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139281.3(WDR36):c.291+209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,162 control chromosomes in the GnomAD database, including 6,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (6001 hom., cov: 32)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.274

Genes affected

WDR36 (HGNC:30696): (WD repeat domain 36) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Mutations in this gene have been associated with adult-onset primary open-angle glaucoma (POAG). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-111097388-A-G is Benign according to our data. Variant chr5-111097388-A-G is described in ClinVar as [Benign]. Clinvar id is 1222031.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR36	NM_139281.3	c.291+209A>G		intron_variant		ENST00000513710.4
WDR36	XM_047416729.1	c.291+209A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR36	ENST00000513710.4	c.291+209A>G		intron_variant		1	NM_139281.3	P1
WDR36	ENST00000504122.2	n.173+209A>G		intron_variant, non_coding_transcript_variant		4
WDR36	ENST00000505303.5	n.427+209A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39349 AN: 152044 Hom.: 6005 Cov.: 32

Gnomad AFR AF: 0.0976

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.258 AC: 39332 AN: 152162 Hom.: 6001 Cov.: 32 AF XY: 0.266 AC XY: 19787 AN XY: 74390

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.277

Alfa AF: 0.269 Hom.: 769

Bravo AF: 0.245

Asia WGS AF: 0.293 AC: 1020 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.7
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: rs13185610; hg19: chr5-110433086; COSMIC: COSV72411559; COSMIC: COSV72411559;