18-49267201-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001353214.3(DYM):c.1251+4977T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.52 (8843 hom., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYM	NM_001353214.3	c.1251+4977T>A		intron_variant		ENST00000675505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYM	ENST00000675505.1	c.1251+4977T>A		intron_variant			NM_001353214.3
DYM	ENST00000269445.10	c.1251+4977T>A		intron_variant		1		P1
DYM	ENST00000442713.6	c.681+4977T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 51128 AN: 98264 Hom.: 8830 Cov.: 22 FAILED QC

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.527

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.526

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.520 AC: 51187 AN: 98368 Hom.: 8843 Cov.: 22 AF XY: 0.519 AC XY: 25241 AN XY: 48666

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.4
Dann	Benign	0.14

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: rs473376; hg19: chr18-46793571; COSMIC: COSV53988610;