17-1716626-C-T

Variant names:

• chr17-1716626-C-T
• rs201917309
• ENST00000446363:c.-397C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001163673.2(WDR81):​c.51C>T​(p.Ser17Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,551,704 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (6 hom.)
• Consequence: WDR81 NM_001163673.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.554

Genes affected

WDR81 (HGNC:26600): (WD repeat domain 81) This gene encodes a multi-domain transmembrane protein which is predominantly expressed in the brain and is thought to play a role in endolysosomal trafficking. Mutations in this gene are associated with an autosomal recessive form of a syndrome exhibiting cerebellar ataxia, cognitive disability, and disequilibrium (CAMRQ2). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

MIR22HG (HGNC:28219): (MIR22 host gene) Predicted to act upstream of or within response to wounding. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00956881).
• BP6: Variant 17-1716626-C-T is Benign according to our data. Variant chr17-1716626-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2578776.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-1716626-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.554 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00209 (319/152396) while in subpopulation NFE AF = 0.00357 (243/68034). AF 95% confidence interval is 0.0032. There are 0 homozygotes in GnomAd4. There are 139 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR81	NM_001163673.2	c.51C>T	p.Ser17Ser	synonymous_variant	Exon 1 of 10		NP_001157145.1
WDR81	NM_152348.4	c.-131C>T		5_prime_UTR_variant	Exon 1 of 11		NP_689561.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR81	ENST00000446363	c.-397C>T		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000401560.1
WDR81	ENST00000468539.5	c.55C>T	p.Arg19Cys	missense_variant	Exon 1 of 4	4		ENSP00000460742.1
WDR81	ENST00000437219.6	c.51C>T	p.Ser17Ser	synonymous_variant	Exon 1 of 10	2		ENSP00000391074.2

Frequencies

GnomAD3 genomes AF: 0.00209 AC: 319 AN: 152278 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00357

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00187 AC: 293 AN: 156536 AF XY: 0.00183

Gnomad AFR exome AF: 0.000253

Gnomad AMR exome AF: 0.000932

Gnomad ASJ exome AF: 0.00141

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00250

Gnomad NFE exome AF: 0.00315

Gnomad OTH exome AF: 0.00159

GnomAD4 exome AF: 0.00334 AC: 4676 AN: 1399308 Hom.: 6 Cov.: 30 AF XY: 0.00317 AC XY: 2190 AN XY: 690146

Gnomad4 AFR exome AF: 0.000411 AC: 13 AN: 31598

Gnomad4 AMR exome AF: 0.00112 AC: 40 AN: 35700

Gnomad4 ASJ exome AF: 0.00111 AC: 28 AN: 25182

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35738

Gnomad4 SAS exome AF: 0.00126 AC: 100 AN: 79230

Gnomad4 FIN exome AF: 0.00266 AC: 131 AN: 49206

Gnomad4 NFE exome AF: 0.00385 AC: 4157 AN: 1078958

Gnomad4 Remaining exome AF: 0.00350 AC: 203 AN: 57998

GnomAD4 genome AF: 0.00209 AC: 319 AN: 152396 Hom.: 0 Cov.: 33 AF XY: 0.00187 AC XY: 139 AN XY: 74528

Gnomad4 AFR AF: 0.000457 AC: 0.000456731 AN: 0.000456731

Gnomad4 AMR AF: 0.00124 AC: 0.00124069 AN: 0.00124069

Gnomad4 ASJ AF: 0.00173 AC: 0.00172811 AN: 0.00172811

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00103 AC: 0.00103434 AN: 0.00103434

Gnomad4 FIN AF: 0.00216 AC: 0.00216409 AN: 0.00216409

Gnomad4 NFE AF: 0.00357 AC: 0.00357174 AN: 0.00357174

Gnomad4 OTH AF: 0.00142 AC: 0.00141777 AN: 0.00141777

Alfa AF: 0.00211 Hom.: 0

Bravo AF: 0.00184

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.000723 AC: 1

ESP6500EA AF: 0.00346 AC: 11

ExAC AF: 0.00118 AC: 29

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

WDR81: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.030	T
FATHMM_MKL	Uncertain	0.80	D
MetaRNN	Benign	0.0096	T
MVP		0.68
GERP RS		-1.1
Mutation Taster		=299/1	polymorphism

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201917309; hg19: chr17-1619920; COSMIC: COSV58482580; COSMIC: COSV58482580;