dbSNP rs1422714646: DCAF12L2:p.Leu461Phe (chrX-126164544-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001013628.3(DCAF12L2):c.1381C>T(p.Leu461Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,094,864 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L461V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

DCAF12L2
NM_001013628.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.58

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF12L2	NM_001013628.3 link	c.1381C>T	p.Leu461Phe	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.1381C>T	p.Leu461Phe	missense_variant	Exon 1 of 1	6	NM_001013628.3	ENSP00000353128.2		Q5VW00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.13e-7

AC:

AN:

1094864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

360810

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26356

American (AMR)

AF:

0.00

AC:

AN:

34926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19112

East Asian (EAS)

AF:

0.00

AC:

AN:

30186

South Asian (SAS)

AF:

0.00

AC:

AN:

53590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40445

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3771

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

840585

Other (OTH)

AF:

0.00

AC:

AN:

45893

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

7.6

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.19

Sift

Uncertain

0.024

Sift4G

Uncertain

0.037

Polyphen

0.027

Vest4

0.86

MutPred

0.29

Loss of disorder (P = 0.1718);

MVP

0.70

ClinPred

0.92

GERP RS

3.9

Varity_R

0.48

gMVP

0.74

Mutation Taster

=59/41

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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rs1422714646

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over