dbSNP rs200667384: DCAF12L2:p.Phe270Cys (chrX-126165116-A-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001013628.3(DCAF12L2):c.809T>G(p.Phe270Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000397 in 1,210,663 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 174 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 12 hem., cov: 26)

Exomes 𝑓: 0.00040 ( 0 hom. 162 hem. )

Consequence

DCAF12L2
NM_001013628.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.24

Publications

1 publications found

Variant links:

Genes affected

DCAF12L2 (HGNC:32950): (DDB1 and CUL4 associated factor 12 like 2) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by Gly-His and Trp-Asp (GH-WD), which may facilitate formation of heterotrimeric or multi-protein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene appears to represent an intronless retrocopy of a related multi-exon gene located on chromosome 9. However, the CDS of this intronless gene remains intact, it is conserved in other mammalian species, it is known to be transcribed, and it is therefore thought to encode a functional protein. [provided by RefSeq, May 2010]

DCAF12L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09553155).

BP6

Variant X-126165116-A-C is Benign according to our data. Variant chrX-126165116-A-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2661381.

BS2

High Hemizygotes in GnomAd4 at 12 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013628.3. 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
	DCAF12L2	NM_001013628.3	MANE Select	c.809T>G	p.Phe270Cys	missense	Exon 1 of 1	NP_001013650.1	Q5VW00

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF12L2	ENST00000360028.4	TSL:6 MANE Select	c.809T>G	p.Phe270Cys	missense	Exon 1 of 1	ENSP00000353128.2	Q5VW00

Frequencies

GnomAD3 genomes

AF:

0.000398

AC:

AN:

112938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000643

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000554

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00127

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000525

Gnomad OTH

AF:

0.000654

GnomAD2 exomes

AF:

0.000485

AC:

AN:

181573

AF XY:

0.000391

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000731

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00151

Gnomad NFE exome

AF:

0.000741

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.000397

AC:

436

AN:

1097725

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

162

AN XY:

363111

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26402

American (AMR)

AF:

0.000142

AC:

AN:

35188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19310

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000370

AC:

AN:

54063

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

40492

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.000435

AC:

366

AN:

841861

Other (OTH)

AF:

0.000347

AC:

AN:

46075

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000398

AC:

AN:

112938

Hom.:

Cov.:

AF XY:

0.000342

AC XY:

AN XY:

35084

show subpopulations

African (AFR)

AF:

0.0000643

AC:

AN:

31098

American (AMR)

AF:

0.000554

AC:

AN:

10829

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2662

East Asian (EAS)

AF:

0.00

AC:

AN:

3537

South Asian (SAS)

AF:

0.00

AC:

AN:

2780

European-Finnish (FIN)

AF:

0.00127

AC:

AN:

6292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000525

AC:

AN:

53286

Other (OTH)

AF:

0.000654

AC:

AN:

1530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.0000651

Hom.:

Bravo

AF:

0.000389

ExAC

AF:

0.000511

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Pathogenic

0.20

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.32

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.72

M_CAP

Benign

0.058

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.3

PhyloP100

5.2

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.5

REVEL

Uncertain

0.47

Sift

Benign

0.055

Sift4G

Uncertain

0.051

Polyphen

0.090

Vest4

0.52

MVP

0.71

ClinPred

0.10

GERP RS

3.4

Varity_R

0.34

gMVP

0.94

Mutation Taster

=87/13

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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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