Variant 1-168045209-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PP5_ModerateBP4BS2_Supporting

The NM_001198956.2(DCAF6):c.2240G>A(p.Arg747Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000498 in 1,607,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

DCAF6
NM_001198956.2 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.20

Variant links:

Genes affected

DCAF6 (HGNC:30002): (DDB1 and CUL4 associated factor 6) The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]

DCAF6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5

Variant 1-168045209-G-A is Pathogenic according to our data. Variant chr1-168045209-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 224814.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-168045209-G-A is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.14479268). . Strength limited to SUPPORTING due to the PP5.

BS2

High AC in GnomAd4 at 57 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCAF6	NM_001198956.2 linkuse as main transcript	c.2240G>A	p.Arg747Gln	missense_variant	16/22	ENST00000367840.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCAF6	ENST00000367840.4 linkuse as main transcript	c.2240G>A	p.Arg747Gln	missense_variant	16/22	1	NM_001198956.2		Q58WW2-3

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000720

AC:

176

AN:

244578

Hom.:

AF XY:

0.000763

AC XY:

101

AN XY:

132386

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.000209

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.000577

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.000959

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.000510

AC:

743

AN:

1455566

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

400

AN XY:

723534

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.000194

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000764

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.000482

Gnomad4 OTH exome

AF:

0.000832

GnomAD4 genome

AF:

0.000375

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000762

Hom.:

Bravo

AF:

0.000525

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000667

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.00119

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cerebral visual impairment and intellectual disability

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Sep 09, 2015

This study shows that diverse genetic causes underlie CVI. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

.;.;T;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.5

.;.;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Uncertain

0.45

Sift

Uncertain

0.012

D;T;D;D

Sift4G

Uncertain

0.034

D;T;T;D

Polyphen

1.0

.;D;D;D

Vest4

0.60

MVP

0.58

MPC

1.2

ClinPred

0.36

GERP RS

4.5

Varity_R

0.14

gMVP

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over