dbSNP rs587780328: DCAF17:c.1183-6T>C (chr2-171477981-T-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_025000.4(DCAF17):c.1183-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000783 in 1,609,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

DCAF17
NM_025000.4 splice_region, intron

Scores

Splicing: ADA: 0.0002899

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.45

Publications

0 publications found

Variant links:

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: Genomics England PanelApp, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P

DCAF17 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_025000.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-171477981-T-C is Benign according to our data. Variant chr2-171477981-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 128886.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DCAF17	NM_025000.4	MANE Select	c.1183-6T>C	splice_region intron	N/A	NP_079276.2	Q5H9S7-1
DCAF17	NM_001164821.2		c.982-6T>C	splice_region intron	N/A	NP_001158293.1	F5H7W1
DCAF17	NR_028482.2		n.1429-6T>C	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DCAF17	ENST00000375255.8	TSL:1 MANE Select	c.1183-6T>C	splice_region intron	N/A	ENSP00000364404.3	Q5H9S7-1
DCAF17	ENST00000339506.7	TSL:1	c.433-6T>C	splice_region intron	N/A	ENSP00000342160.3	H0Y2X0
DCAF17	ENST00000966668.1		c.1234-6T>C	splice_region intron	N/A	ENSP00000636727.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000597

AC:

AN:

251192

AF XY:

0.0000589

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000858

AC:

125

AN:

1456848

Hom.:

Cov.:

AF XY:

0.0000883

AC XY:

AN XY:

725156

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33364

American (AMR)

AF:

0.00

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000111

AC:

123

AN:

1107544

Other (OTH)

AF:

0.0000166

AC:

AN:

60188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000740

Hom.:

Bravo

AF:

0.0000189

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Woodhouse-Sakati syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

1.5

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00029

dbscSNV1_RF

Benign

0.094

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over