NM_025000.4:c.939G>A

Variant names:

• chr2-171468988-G-A
• rs61731491
• NM_025000.4:c.939G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_025000.4(DCAF17):​c.939G>A​(p.Gln313Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00766 in 1,614,050 control chromosomes in the GnomAD database, including 722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (394 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (328 hom.)
• Consequence: DCAF17 NM_025000.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.324
• Publications: 1 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.098).
• BP6: Variant 2-171468988-G-A is Benign according to our data. Variant chr2-171468988-G-A is described in ClinVar as Benign. ClinVar VariationId is 128891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.324 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025000.4. 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.939G>A	p.Gln313Gln	synonymous	Exon 9 of 14	NP_079276.2
	DCAF17	NM_001164821.2		c.939G>A	p.Gln313Gln	synonymous	Exon 9 of 12	NP_001158293.1
	DCAF17	NR_028482.2		n.1185G>A		non_coding_transcript_exon	Exon 8 of 13

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF17	ENST00000375255.8	TSL:1 MANE Select	c.939G>A	p.Gln313Gln	synonymous	Exon 9 of 14	ENSP00000364404.3
	DCAF17	ENST00000339506.7	TSL:1	c.189G>A	p.Gln63Gln	synonymous	Exon 2 of 7	ENSP00000342160.3
	DCAF17	ENST00000611110.4	TSL:1	c.99G>A	p.Gln33Gln	synonymous	Exon 3 of 8	ENSP00000477604.1

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6023 AN: 152150 Hom.: 395 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.0297

GnomAD2 exomes AF: 0.0110 AC: 2769 AN: 251188 AF XY: 0.00825

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.00888

Gnomad ASJ exome AF: 0.00645

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000687

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00434 AC: 6342 AN: 1461782 Hom.: 328 Cov.: 31 AF XY: 0.00380 AC XY: 2763 AN XY: 727186

African (AFR) AF: 0.136 AC: 4543 AN: 33470

American (AMR) AF: 0.00975 AC: 436 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 173 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000441 AC: 38 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.0109 AC: 63 AN: 5766

European-Non Finnish (NFE) AF: 0.000435 AC: 484 AN: 1111956

Other (OTH) AF: 0.0100 AC: 604 AN: 60392

GnomAD4 genome AF: 0.0395 AC: 6022 AN: 152268 Hom.: 394 Cov.: 32 AF XY: 0.0386 AC XY: 2875 AN XY: 74454

African (AFR) AF: 0.132 AC: 5496 AN: 41526

American (AMR) AF: 0.0242 AC: 371 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000853 AC: 58 AN: 68024

Other (OTH) AF: 0.0294 AC: 62 AN: 2112

Alfa AF: 0.0216 Hom.: 165

Bravo AF: 0.0451

Asia WGS AF: 0.00751 AC: 27 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Woodhouse-Sakati syndrome Benign:3

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

Mutations in DCAF17 have been associated with a rare syndrome called Woodhouse Sakati Syndrome, which can have diabetes mellitus as one of the presentations.However no sufficient evidence is found to ascertain the role of this particular variant rs61731491, yet.

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Mar 05, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.6
DANN	Benign	0.51
PhyloP100		0.32
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: rs61731491; hg19: chr2-172325498; COSMIC: COSV59829555; COSMIC: COSV59829555;