DYM p.Val685Leu

Variant names:

• chr18-49044177-C-A
• NM_001353214.3:c.2053G>T
• DYM p.Val685Leu

Your query was ambiguous. Multiple possible variants found:

• chr18-49044177-C-A
• chr18-49044177-C-G
• chr18-49044175-CAC-TAA
• chr18-49044175-CAC-AAG
• chr18-49044175-CAC-GAG
• chr18-49044175-CAC-TAG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001353214.3(DYM):​c.2053G>T​(p.Val685Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. V685M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DYM NM_001353214.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.72
• Publications: 0 publications found

Genes affected

DYM (HGNC:21317): (dymeclin) This gene encodes a protein which regulates Golgi-associated secretory pathways that are essential to endochondral bone formation during early development. This gene is also believed to play a role in early brain development. This gene is widely expressed in embryos and is particularly abundant in chodrocytes and brain tissues. It encodes a peripheral membrane protein which shuttles between the cytosol and Golgi complex. Mutations in this gene are associated with two types of recessive osteochondrodysplasia: Dyggve-Melchior-Clausen (DMC) dysplasia and Smith-McCort (SMC) dysplasia. [provided by RefSeq, Jun 2017]

DYM-AS1 (HGNC:37046): (DYM antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.804

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353214.3. 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
	DYM	NM_001353214.3	MANE Select	c.2053G>T	p.Val685Leu	missense	Exon 18 of 18	NP_001340143.1	A0A6Q8PF81
	DYM	NM_001374428.1		c.2053G>T	p.Val685Leu	missense	Exon 19 of 19	NP_001361357.1	A0A6Q8PF81
	DYM	NM_001353212.3		c.2050G>T	p.Val684Leu	missense	Exon 18 of 18	NP_001340141.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYM	ENST00000675505.1	MANE Select	c.2053G>T	p.Val685Leu	missense	Exon 18 of 18	ENSP00000501694.1	A0A6Q8PF81
	DYM	ENST00000269445.10	TSL:1	c.1888G>T	p.Val630Leu	missense	Exon 17 of 17	ENSP00000269445.6	Q7RTS9-1
	DYM	ENST00000919568.1		c.1888G>T	p.Val630Leu	missense	Exon 17 of 17	ENSP00000589627.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.57	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.039	D
Varity_R		0.60
gMVP		0.39
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr18-46570547;