4-39266152-G-C

Variant names:

• chr4-39266152-G-C
• rs137960733
• NM_025132.4:c.3261+12G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025132.4(WDR19):​c.3261+12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,788 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: WDR19 NM_025132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR19	NM_025132.4	c.3261+12G>C		intron_variant	Intron 29 of 36	ENST00000399820.8	NP_079408.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR19	ENST00000399820.8	c.3261+12G>C		intron_variant	Intron 29 of 36	1	NM_025132.4	ENSP00000382717.3
WDR19	ENST00000506869.5	n.*2842+12G>C		intron_variant	Intron 28 of 35	2		ENSP00000424319.1
WDR19	ENST00000512095.5	n.2259+12G>C		intron_variant	Intron 19 of 22	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000623 AC: 1 AN: 160532 AF XY: 0.00

Gnomad AFR exome AF: 0.000112

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1387788 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 682752

African (AFR) AF: 0.0000317 AC: 1 AN: 31506

American (AMR) AF: 0.00 AC: 0 AN: 34874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24838

East Asian (EAS) AF: 0.00 AC: 0 AN: 35912

South Asian (SAS) AF: 0.00 AC: 0 AN: 76718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070980

Other (OTH) AF: 0.00 AC: 0 AN: 57674

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.54
DANN	Benign	0.39
PhyloP100		-0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs137960733; hg19: chr4-39267772;