rs199690770

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001013628.3(DCAF12L2):c.811A>G(p.Ser271Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,210,591 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 172 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 24)

Exomes 𝑓: 0.00040 ( 0 hom. 160 hem. )

Consequence

DCAF12L2
NM_001013628.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.51

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037723094).

BP6

Variant X-126165114-T-C is Benign according to our data. Variant chrX-126165114-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2661380.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF12L2	NM_001013628.3 link	c.811A>G	p.Ser271Gly	missense_variant	Exon 1 of 1	ENST00000360028.4	NP_001013650.1	Q5VW00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF12L2	ENST00000360028.4 link	c.811A>G	p.Ser271Gly	missense_variant	Exon 1 of 1	6	NM_001013628.3	ENSP00000353128.2		Q5VW00

Frequencies

GnomAD3 genomes

AF:

0.000399

AC:

AN:

112872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000643

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000555

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:

0.000526

Gnomad OTH

AF:

0.000654

GnomAD2 exomes

AF:

0.000479

AC:

AN:

181572

AF XY:

0.000376

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:

0.000395

AC:

434

AN:

1097719

Hom.:

Cov.:

AF XY:

0.000441

AC XY:

160

AN XY:

363105

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26399

American (AMR)

AF:

0.000142

AC:

AN:

35189

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19315

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54057

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

40491

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.000435

AC:

366

AN:

841857

Other (OTH)

AF:

0.000347

AC:

AN:

46075

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000399

AC:

AN:

112872

Hom.:

Cov.:

AF XY:

0.000342

AC XY:

AN XY:

35038

show subpopulations

African (AFR)

AF:

0.0000643

AC:

AN:

31107

American (AMR)

AF:

0.000555

AC:

AN:

10816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2662

East Asian (EAS)

AF:

0.00

AC:

AN:

3536

South Asian (SAS)

AF:

0.00

AC:

AN:

2779

European-Finnish (FIN)

AF:

0.00127

AC:

AN:

6281

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000526

AC:

AN:

53238

Other (OTH)

AF:

0.000654

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000354

Hom.:

Bravo

AF:

0.000389

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000511

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 01, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.811A>G (p.S271G) alteration is located in exon 1 (coding exon 1) of the DCAF12L2 gene. This alteration results from a A to G substitution at nucleotide position 811, causing the serine (S) at amino acid position 271 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DCAF12L2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.56

M_CAP

Benign

0.024

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.7

PhyloP100

3.5

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.2

REVEL

Benign

0.21

Sift

Benign

0.13

Sift4G

Benign

0.25

Polyphen

0.0020

Vest4

0.17

MVP

0.53

ClinPred

0.021

GERP RS

3.4

Varity_R

0.11

gMVP

0.80

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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rs199690770

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