chr8-87872875-A-G

Position:

• chr8-87872875-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152418.4(DCAF4L2):​c.1097T>C​(p.Val366Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCAF4L2 NM_152418.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.92

Genes affected

DCAF4L2 (HGNC:26657): (DDB1 and CUL4 associated factor 4 like 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF4L2	NM_152418.4	c.1097T>C	p.Val366Ala	missense_variant	1/1	ENST00000319675.5	NP_689631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF4L2	ENST00000319675.5	c.1097T>C	p.Val366Ala	missense_variant	1/1	6	NM_152418.4	ENSP00000316496.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.1097T>C (p.V366A) alteration is located in exon 1 (coding exon 1) of the DCAF4L2 gene. This alteration results from a T to C substitution at nucleotide position 1097, causing the valine (V) at amino acid position 366 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.023
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0043	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.30
Sift	Benign	0.18	T
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.80		Gain of sheet (P = 0.0101);
MVP		0.75
MPC		0.63
ClinPred		0.96	D
GERP RS		1.4
Varity_R		0.14
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-88885103;