18-49092458-T-G

Position:

• chr18-49092458-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353214.3(DYM):​c.2025+4944A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,140 control chromosomes in the GnomAD database, including 2,884 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2884 hom., cov: 32)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYM	NM_001353214.3	c.2025+4944A>C		intron_variant		ENST00000675505.1	NP_001340143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYM	ENST00000675505.1	c.2025+4944A>C		intron_variant			NM_001353214.3	ENSP00000501694
DYM	ENST00000269445.10	c.1860+4944A>C		intron_variant		1		ENSP00000269445	P1
DYM	ENST00000442713.6	c.1290+4944A>C		intron_variant		2		ENSP00000395942
DYM	ENST00000577734.1	c.187+759A>C		intron_variant		3		ENSP00000464163

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23270 AN: 152022 Hom.: 2881 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0567

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.153 AC: 23292 AN: 152140 Hom.: 2884 Cov.: 32 AF XY: 0.156 AC XY: 11599 AN XY: 74376

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0567

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.0866

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.0586

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0672 Hom.: 712

Bravo AF: 0.160

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.66

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

LitVar

Other links and lift over

dbSNP: rs7239949; hg19: chr18-46618828;