2-171477879-G-A

Variant names:

• chr2-171477879-G-A
• rs146683580
• NM_025000.4:c.1183-108G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_025000.4(DCAF17):​c.1183-108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00972 in 828,710 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (9 hom., cov: 32)
  • Exomes 𝑓: 0.010 (45 hom.)
• Consequence: DCAF17 NM_025000.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.292

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-171477879-G-A is Benign according to our data. Variant chr2-171477879-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1190346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00859 (1308/152338) while in subpopulation NFE AF= 0.013 (886/68030). AF 95% confidence interval is 0.0123. There are 9 homozygotes in gnomad4. There are 601 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF17	NM_025000.4	c.1183-108G>A		intron_variant	Intron 11 of 13	ENST00000375255.8	NP_079276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF17	ENST00000375255.8	c.1183-108G>A		intron_variant	Intron 11 of 13	1	NM_025000.4	ENSP00000364404.3

Frequencies

GnomAD3 genomes AF: 0.00860 AC: 1309 AN: 152220 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.00998 AC: 6749 AN: 676372 Hom.: 45 AF XY: 0.00986 AC XY: 3549 AN XY: 359802

Gnomad4 AFR exome AF: 0.00246

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.0188

Gnomad4 EAS exome AF: 0.0000930

Gnomad4 SAS exome AF: 0.000924

Gnomad4 FIN exome AF: 0.00137

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.00859 AC: 1308 AN: 152338 Hom.: 9 Cov.: 32 AF XY: 0.00807 AC XY: 601 AN XY: 74504

Gnomad4 AFR AF: 0.00252

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00969 Hom.: 3

Bravo AF: 0.00965

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs146683580; hg19: chr2-172334389;