4-39255344-G-T

Variant names:

• chr4-39255344-G-T
• rs6831700
• NM_025132.4:c.3002-504G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025132.4(WDR19):​c.3002-504G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,994 control chromosomes in the GnomAD database, including 26,137 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 0.55 (26137 hom., cov: 31)
• Consequence: WDR19 NM_025132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414
• Publications: 6 publications found

Genes affected

WDR19 (HGNC:18340): (WD repeat domain 19) The protein encoded by this gene is a member of the WD (tryptophan-aspartic acid) repeat family, which is a large family of structurally-related proteins known to participate in a wide range of cellular processes. Each WD repeat typically contains about 40 amino acids that are usually bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. This protein contains six WD repeats, three transmembrane domains, and a clathrin heavy-chain repeat. Mutations in this gene have been described in individuals with a wide range of disorders affecting function of the cilium. These disorders are known as ciliopathies, and include Jeune syndrome, Sensenbrenner syndromes, Senior-Loken syndrome, combined or isolated nephronophthisis (NPHP), and retinitis pigmentosa (RP). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

WDR19 Gene-Disease associations (from GenCC):

• asphyxiating thoracic dystrophy 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cranioectodermal dysplasia 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• nephronophthisis 13

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Senior-Loken syndrome 8

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• cranioectodermal dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR19	NM_025132.4	c.3002-504G>T		intron_variant	Intron 26 of 36	ENST00000399820.8	NP_079408.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR19	ENST00000399820.8	c.3002-504G>T		intron_variant	Intron 26 of 36	1	NM_025132.4	ENSP00000382717.3
WDR19	ENST00000506869.5	n.*2583-504G>T		intron_variant	Intron 25 of 35	2		ENSP00000424319.1
WDR19	ENST00000512095.5	n.2000-504G>T		intron_variant	Intron 16 of 22	2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83483 AN: 151876 Hom.: 26122 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.550 AC: 83521 AN: 151994 Hom.: 26137 Cov.: 31 AF XY: 0.553 AC XY: 41102 AN XY: 74264

African (AFR) AF: 0.226 AC: 9352 AN: 41458

American (AMR) AF: 0.662 AC: 10095 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2278 AN: 3468

East Asian (EAS) AF: 0.823 AC: 4252 AN: 5164

South Asian (SAS) AF: 0.706 AC: 3393 AN: 4804

European-Finnish (FIN) AF: 0.615 AC: 6495 AN: 10554

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45701 AN: 67982

Other (OTH) AF: 0.586 AC: 1234 AN: 2106

Alfa AF: 0.610 Hom.: 8013

Bravo AF: 0.539

Asia WGS AF: 0.744 AC: 2586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.52
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6831700; hg19: chr4-39256964;