rs2037852520

Variant names:

• chr14-69054057-T-C
• rs2037852520
• NM_003861.3:c.2629A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-69054057-T-C
• chr14-69054057-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003861.3(DCAF5):​c.2629A>G​(p.Thr877Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. T877I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCAF5 NM_003861.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• Publications: 0 publications found

Genes affected

DCAF5 (HGNC:20224): (DDB1 and CUL4 associated factor 5) Predicted to be involved in protein ubiquitination. Part of Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036206603).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003861.3. 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
	DCAF5	NM_003861.3	MANE Select	c.2629A>G	p.Thr877Ala	missense	Exon 9 of 9	NP_003852.1	Q96JK2-1
	DCAF5	NM_001284206.1		c.2626A>G	p.Thr876Ala	missense	Exon 9 of 9	NP_001271135.1	Q96JK2-3
	DCAF5	NM_001284207.1		c.2383A>G	p.Thr795Ala	missense	Exon 9 of 9	NP_001271136.1	Q96JK2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF5	ENST00000341516.10	TSL:1 MANE Select	c.2629A>G	p.Thr877Ala	missense	Exon 9 of 9	ENSP00000341351.5	Q96JK2-1
	DCAF5	ENST00000557386.5	TSL:1	c.2626A>G	p.Thr876Ala	missense	Exon 9 of 9	ENSP00000451845.1	Q96JK2-3
	DCAF5	ENST00000554215.5	TSL:1	c.2383A>G	p.Thr795Ala	missense	Exon 9 of 9	ENSP00000451551.1	Q96JK2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461724 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.26	N
PhyloP100		0.38
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.065
Sift	Benign	0.37	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.068
MutPred		0.14		Loss of sheet (P = 0.007)
MVP		0.15
MPC		0.20
ClinPred		0.042	T
GERP RS		2.7
Varity_R		0.020
gMVP		0.064
Mutation Taster		=98/2	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: rs2037852520; hg19: chr14-69520774;