Variant 8-87873137-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_152418.4(DCAF4L2):c.835C>T(p.Leu279Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000515 in 1,614,192 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 4 hom. )

Consequence

DCAF4L2
NM_152418.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.97

Variant links:

Genes affected

DCAF4L2 (HGNC:26657): (DDB1 and CUL4 associated factor 4 like 2)

DCAF4L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006407976).

BP6

Variant 8-87873137-G-A is Benign according to our data. Variant chr8-87873137-G-A is described in ClinVar as [Benign]. Clinvar id is 3037956.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF4L2	NM_152418.4 linkuse as main transcript	c.835C>T	p.Leu279Phe	missense_variant	1/1	ENST00000319675.5	NP_689631.1	Q8NA75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF4L2	ENST00000319675.5 linkuse as main transcript	c.835C>T	p.Leu279Phe	missense_variant	1/1	6	NM_152418.4	ENSP00000316496.3		Q8NA75

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

337

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000593

AC:

149

AN:

251330

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.00763

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000339

AC:

495

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

218

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00696

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.00221

AC:

337

AN:

152302

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00770

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.00235

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000741

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DCAF4L2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0064

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.18

Sift

Uncertain

0.028

Sift4G

Uncertain

0.044

Polyphen

0.18

Vest4

0.24

MVP

0.51

MPC

0.38

ClinPred

0.093

GERP RS

0.75

Varity_R

0.17

gMVP

0.21

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