18-67512592-G-C

Variant names:

• chr18-67512592-G-C
• rs2279269
• NM_032160.3:c.2017C>G

Variant summary

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

The NM_032160.3(DSEL):​c.2017C>G​(p.Pro673Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DSEL NM_032160.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 29 publications found

Genes affected

DSEL (HGNC:18144): (dermatan sulfate epimerase like) Predicted to enable chondroitin-glucuronate 5-epimerase activity. Predicted to be involved in chondroitin sulfate metabolic process and dermatan sulfate metabolic process. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000263424 (HGNC:):

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=0.052227348).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032160.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSEL	NM_032160.3	MANE Select	c.2017C>G	p.Pro673Ala	missense	Exon 2 of 2	NP_115536.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSEL	ENST00000310045.9	TSL:2 MANE Select	c.2017C>G	p.Pro673Ala	missense	Exon 2 of 2	ENSP00000310565.8
	ENSG00000263424	ENST00000583493.1	TSL:5	n.1851G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 46

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	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	16
DANN	Benign	0.78
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.37	N
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.041
Sift	Benign	0.38	T
Sift4G	Benign	0.75	T
Vest4		0.052
MVP		0.11
MPC		0.12
ClinPred		0.073	T
GERP RS		2.9
gMVP		0.24
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2279269; hg19: chr18-65179829;