rs192861143

Variant names:

• chr2-171448667-C-A
• rs192861143
• NM_025000.4:c.322-14C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-171448667-C-A
• chr2-171448667-C-T

Variant summary

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

The ENST00000375255.8(DCAF17):​c.322-14C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000846 in 1,182,586 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: 8.5e-7 (0 hom.)
• Consequence: DCAF17 ENST00000375255.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977
• Publications: 0 publications found

Genes affected

DCAF17 (HGNC:25784): (DDB1 and CUL4 associated factor 17) This gene encodes a nuclear transmembrane protein that associates with cullin 4A/damaged DNA binding protein 1 ubiquitin ligase complex. Mutations in this gene are associated with Woodhouse-Sakati syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

DCAF17 Gene-Disease associations (from GenCC):

• Woodhouse-Sakati syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, ClinGen, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

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=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375255.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF17	NM_025000.4	MANE Select	c.322-14C>A		intron	N/A	NP_079276.2
	DCAF17	NM_001164821.2		c.322-14C>A		intron	N/A	NP_001158293.1
	DCAF17	NR_028482.2		n.674-14C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF17	ENST00000375255.8	TSL:1 MANE Select	c.322-14C>A		intron	N/A	ENSP00000364404.3
	DCAF17	ENST00000539783.5	TSL:5	c.322-14C>A		intron	N/A	ENSP00000442238.1
	DCAF17	ENST00000436317.1	TSL:4	n.353-14C>A		intron	N/A	ENSP00000400335.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.46e-7 AC: 1 AN: 1182586 Hom.: 0 Cov.: 31 AF XY: 0.00000171 AC XY: 1 AN XY: 585580

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25406

American (AMR) AF: 0.00 AC: 0 AN: 27722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20760

East Asian (EAS) AF: 0.00 AC: 0 AN: 33538

South Asian (SAS) AF: 0.0000155 AC: 1 AN: 64686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4604

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 913334

Other (OTH) AF: 0.00 AC: 0 AN: 48560

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.20
PhyloP100		-0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs192861143; hg19: chr2-172305177;