Genetic Variant DCAF4L2:p.Leu276Leu (chr8-87873146-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_152418.4(DCAF4L2):c.826C>T(p.Leu276Leu) 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 1,614,196 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 8 hom. )

Consequence

DCAF4L2
NM_152418.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.38

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 8-87873146-G-A is Benign according to our data. Variant chr8-87873146-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3034793.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF4L2	NM_152418.4 link	c.826C>T	p.Leu276Leu	synonymous_variant	Exon 1 of 1	ENST00000319675.5	NP_689631.1	Q8NA75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF4L2	ENST00000319675.5 link	c.826C>T	p.Leu276Leu	synonymous_variant	Exon 1 of 1	6	NM_152418.4	ENSP00000316496.3		Q8NA75

Frequencies

GnomAD3 genomes

AF:

0.000769

AC:

117

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000999

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00123

AC:

309

AN:

251336

AF XY:

0.00136

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00130

AC:

1896

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

993

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.00210

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00248

AC:

214

AN:

86258

European-Finnish (FIN)

AF:

0.000693

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00131

AC:

1461

AN:

1112010

Other (OTH)

AF:

0.00139

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

136

272

407

543

679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000768

AC:

117

AN:

152310

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41578

American (AMR)

AF:

0.00150

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00100

AC:

AN:

68032

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000736

Hom.:

Bravo

AF:

0.000903

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.000948

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DCAF4L2-related disorder

Benign:1

Jul 25, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.3

(source)

DANN

Benign

0.41

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism

(source)

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

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chr8-87873146-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over