2-171480091-T-C

Variant names:

• chr2-171480091-T-C
• rs3731980
• NM_025000.4:c.1320T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_025000.4(DCAF17):​c.1320T>C​(p.Ala440Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,613,878 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (52 hom.)
• Consequence: DCAF17 NM_025000.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0980
• Publications: 3 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=0.062).
• BP6: Variant 2-171480091-T-C is Benign according to our data. Variant chr2-171480091-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.098 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0019 (289/152344) while in subpopulation EAS AF = 0.0424 (220/5192). AF 95% confidence interval is 0.0378. There are 9 homozygotes in GnomAd4. There are 156 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF17	NM_025000.4	MANE Select	c.1320T>C	p.Ala440Ala	synonymous	Exon 13 of 14	NP_079276.2
	DCAF17	NM_001164821.2		c.1119T>C	p.Ala373Ala	synonymous	Exon 11 of 12	NP_001158293.1
	DCAF17	NR_028482.2		n.1566T>C		non_coding_transcript_exon	Exon 12 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF17	ENST00000375255.8	TSL:1 MANE Select	c.1320T>C	p.Ala440Ala	synonymous	Exon 13 of 14	ENSP00000364404.3
	DCAF17	ENST00000339506.7	TSL:1	c.570T>C	p.Ala190Ala	synonymous	Exon 6 of 7	ENSP00000342160.3
	DCAF17	ENST00000966668.1		c.1371T>C	p.Ala457Ala	synonymous	Exon 14 of 15	ENSP00000636727.1

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 289 AN: 152226 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00279 AC: 701 AN: 250998 AF XY: 0.00257

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0351

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00119 AC: 1735 AN: 1461534 Hom.: 52 Cov.: 31 AF XY: 0.00112 AC XY: 811 AN XY: 727066

African (AFR) AF: 0.000209 AC: 7 AN: 33464

American (AMR) AF: 0.0000895 AC: 4 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0321 AC: 1275 AN: 39672

South Asian (SAS) AF: 0.00108 AC: 93 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5760

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111778

Other (OTH) AF: 0.00543 AC: 328 AN: 60384

GnomAD4 genome AF: 0.00190 AC: 289 AN: 152344 Hom.: 9 Cov.: 32 AF XY: 0.00209 AC XY: 156 AN XY: 74498

African (AFR) AF: 0.000529 AC: 22 AN: 41582

American (AMR) AF: 0.00163 AC: 25 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0424 AC: 220 AN: 5192

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4830

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.000501 Hom.: 1

Bravo AF: 0.00166

Asia WGS AF: 0.0290 AC: 101 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Woodhouse-Sakati syndrome (3)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.0
DANN	Benign	0.60
PhyloP100		0.098
Mutation Taster		=100/0	polymorphism

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: rs3731980; hg19: chr2-172336601;