Genetic Variant DYM:c.1251+4977T>A (chr18-49267201-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.697

Publications

1 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

Dyggve-Melchior-Clausen disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
Smith-McCort dysplasia 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Smith-McCort dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DYM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYM	NM_001353214.3	MANE Select	c.1251+4977T>A	intron	N/A	NP_001340143.1	A0A6Q8PF81
DYM	NM_001374428.1		c.1251+4977T>A	intron	N/A	NP_001361357.1	A0A6Q8PF81
DYM	NM_001353212.3		c.1248+4977T>A	intron	N/A	NP_001340141.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYM	ENST00000675505.1	MANE Select	c.1251+4977T>A	intron	N/A	ENSP00000501694.1	A0A6Q8PF81
DYM	ENST00000269445.10	TSL:1	c.1251+4977T>A	intron	N/A	ENSP00000269445.6	Q7RTS9-1
DYM	ENST00000919568.1		c.1251+4977T>A	intron	N/A	ENSP00000589627.1

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

51128

AN:

98264

Hom.:

8830

Cov.:

show subpopulations

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.:

AF XY:

0.519

AC XY:

25241

AN XY:

48666

show subpopulations

African (AFR)

AF:

0.467

AC:

14972

AN:

32058

American (AMR)

AF:

0.604

AC:

6585

AN:

10904

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

714

AN:

1376

East Asian (EAS)

AF:

0.414

AC:

2060

AN:

4978

South Asian (SAS)

AF:

0.512

AC:

1702

AN:

3326

European-Finnish (FIN)

AF:

0.550

AC:

3747

AN:

6814

Middle Eastern (MID)

AF:

0.522

AC:

AN:

136

European-Non Finnish (NFE)

AF:

0.551

AC:

20378

AN:

37004

Other (OTH)

AF:

0.528

AC:

671

AN:

1270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1642

3284

4927

6569

8211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.4

(source)

DANN

Benign

0.14

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over