X-126165116-A-C

Position:

chrX-126165116-A-C

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id is 2661381.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}. Variant chrX-126165116-A-C is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF12L2	NM_001013628.3 link	c.809T>G	p.Phe270Cys	missense_variant	1/1	ENST00000360028.4	NP_001013650.1	Q5VW00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF12L2	ENST00000360028.4 link	c.809T>G	p.Phe270Cys	missense_variant	1/1	6	NM_001013628.3	ENSP00000353128.2		Q5VW00

Frequencies

GnomAD3 genomes

AF:

0.000398

AC:

AN:

112938

Hom.:

Cov.:

AF XY:

0.000342

AC XY:

AN XY:

35084

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

GnomAD3 exomes

AF:

0.000485

AC:

AN:

181573

Hom.:

AF XY:

0.000391

AC XY:

AN XY:

66479

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 SAS exome

AF:

0.0000531

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.000435

Gnomad4 OTH exome

AF:

0.000347

GnomAD4 genome

AF:

0.000398

AC:

AN:

112938

Hom.:

Cov.:

AF XY:

0.000342

AC XY:

AN XY:

35084

show subpopulations

Gnomad4 AFR

AF:

0.0000643

Gnomad4 AMR

AF:

0.000554

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00127

Gnomad4 NFE

AF:

0.000525

Gnomad4 OTH

AF:

0.000654

Alfa

AF:

0.0000707

Hom.:

Bravo

AF:

0.000389

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 08, 2023

The c.809T>G (p.F270C) alteration is located in exon 1 (coding exon 1) of the DCAF12L2 gene. This alteration results from a T to G substitution at nucleotide position 809, causing the phenylalanine (F) at amino acid position 270 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

DCAF12L2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Pathogenic

0.20

CADD

Benign

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

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

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