chrX-126165376-G-C

Variant names:

• chrX-126165376-G-C
• rs775766094
• NM_001013628.3:c.549C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001013628.3(DCAF12L2):​c.549C>G​(p.Asp183Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,210,913 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.000026 (0 hom. 4 hem.)
• Consequence: DCAF12L2 NM_001013628.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.847
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37149507).
• BS2: High Hemizygotes in GnomAdExome4 at 4 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.549C>G	p.Asp183Glu	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.549C>G	p.Asp183Glu	missense	Exon 1 of 1	ENSP00000353128.2	Q5VW00

Frequencies

GnomAD3 genomes AF: 0.00000884 AC: 1 AN: 113153 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000187

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000264 AC: 29 AN: 1097760 Hom.: 0 Cov.: 37 AF XY: 0.0000110 AC XY: 4 AN XY: 363276

African (AFR) AF: 0.00 AC: 0 AN: 26391

American (AMR) AF: 0.00 AC: 0 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3830

European-Non Finnish (NFE) AF: 0.0000333 AC: 28 AN: 842072

Other (OTH) AF: 0.0000217 AC: 1 AN: 46056

GnomAD4 genome AF: 0.00000884 AC: 1 AN: 113153 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 35289

African (AFR) AF: 0.00 AC: 0 AN: 31187

American (AMR) AF: 0.00 AC: 0 AN: 10870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00 AC: 0 AN: 2785

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6309

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000187 AC: 1 AN: 53336

Other (OTH) AF: 0.00 AC: 0 AN: 1534

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.9
DANN	Benign	0.92
DEOGEN2	Benign	0.29	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.85
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.21
Sift	Benign	0.049	D
Sift4G	Benign	0.071	T
Polyphen		0.058	B
Vest4		0.50
MutPred		0.67		Gain of catalytic residue at D183 (P = 0.0185)
MVP		0.72
ClinPred		0.25	T
GERP RS		0.96
Varity_R		0.21
gMVP		0.48
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs775766094; hg19: chrX-125299359;