5-111121006-A-T

Variant names:

• chr5-111121006-A-T
• rs13186912
• NM_139281.3:c.2013A>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_139281.3(WDR36):​c.2013A>T​(p.Val671Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,610,660 control chromosomes in the GnomAD database, including 80,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6073 hom., cov: 32)
  • Exomes 𝑓: 0.31 (74158 hom.)
• Consequence: WDR36 NM_139281.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.955
• Publications: 21 publications found

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]

WDR36 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, G

  Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-111121006-A-T is Benign according to our data. Variant chr5-111121006-A-T is described in ClinVar as Benign. ClinVar VariationId is 262465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.955 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139281.3. 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
	WDR36	NM_139281.3	MANE Select	c.2013A>T	p.Val671Val	synonymous	Exon 19 of 23	NP_644810.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	ENST00000513710.4	TSL:1 MANE Select	c.2013A>T	p.Val671Val	synonymous	Exon 19 of 23	ENSP00000424628.3
	WDR36	ENST00000946910.1		c.2013A>T	p.Val671Val	synonymous	Exon 19 of 23	ENSP00000616969.1
	WDR36	ENST00000856283.1		c.2010A>T	p.Val670Val	synonymous	Exon 19 of 23	ENSP00000526342.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39686 AN: 151916 Hom.: 6077 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.329 AC: 81934 AN: 249122 AF XY: 0.334

Gnomad AFR exome AF: 0.0968

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.313 AC: 456833 AN: 1458626 Hom.: 74158 Cov.: 34 AF XY: 0.317 AC XY: 230081 AN XY: 725656

African (AFR) AF: 0.0927 AC: 3100 AN: 33430

American (AMR) AF: 0.412 AC: 18360 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 10194 AN: 26052

East Asian (EAS) AF: 0.244 AC: 9655 AN: 39590

South Asian (SAS) AF: 0.402 AC: 34566 AN: 85940

European-Finnish (FIN) AF: 0.392 AC: 20935 AN: 53378

Middle Eastern (MID) AF: 0.400 AC: 2296 AN: 5744

European-Non Finnish (NFE) AF: 0.306 AC: 339208 AN: 1109696

Other (OTH) AF: 0.307 AC: 18519 AN: 60264

GnomAD4 genome AF: 0.261 AC: 39669 AN: 152034 Hom.: 6073 Cov.: 32 AF XY: 0.268 AC XY: 19927 AN XY: 74314

African (AFR) AF: 0.100 AC: 4167 AN: 41538

American (AMR) AF: 0.322 AC: 4908 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3468

East Asian (EAS) AF: 0.259 AC: 1340 AN: 5176

South Asian (SAS) AF: 0.394 AC: 1899 AN: 4824

European-Finnish (FIN) AF: 0.406 AC: 4287 AN: 10552

Middle Eastern (MID) AF: 0.434 AC: 126 AN: 290

European-Non Finnish (NFE) AF: 0.306 AC: 20785 AN: 67904

Other (OTH) AF: 0.280 AC: 590 AN: 2108

Alfa AF: 0.299 Hom.: 2342

Bravo AF: 0.248

Asia WGS AF: 0.296 AC: 1029 AN: 3476

EpiCase AF: 0.322

EpiControl AF: 0.316

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Glaucoma 1, open angle, G (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.57
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs13186912; hg19: chr5-110456704; COSMIC: COSV72605226;