Genetic Variant DYM:c.2025+4944A>C (chr18-49092458-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

Publications

6 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: Benign. The variant received -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.

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.2025+4944A>C	intron	N/A	NP_001340143.1	A0A6Q8PF81
DYM	NM_001374428.1		c.2025+4944A>C	intron	N/A	NP_001361357.1	A0A6Q8PF81
DYM	NM_001353212.3		c.2022+4944A>C	intron	N/A	NP_001340141.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYM	ENST00000675505.1	MANE Select	c.2025+4944A>C	intron	N/A	ENSP00000501694.1	A0A6Q8PF81
DYM	ENST00000269445.10	TSL:1	c.1860+4944A>C	intron	N/A	ENSP00000269445.6	Q7RTS9-1
DYM	ENST00000919568.1		c.1860+4944A>C	intron	N/A	ENSP00000589627.1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23270

AN:

152022

Hom.:

2881

Cov.:

show subpopulations

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.:

AF XY:

0.156

AC XY:

11599

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.327

AC:

13550

AN:

41466

American (AMR)

AF:

0.118

AC:

1804

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0567

AC:

197

AN:

3472

East Asian (EAS)

AF:

0.269

AC:

1389

AN:

5166

South Asian (SAS)

AF:

0.0866

AC:

418

AN:

4828

European-Finnish (FIN)

AF:

0.161

AC:

1701

AN:

10592

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0586

AC:

3983

AN:

68014

Other (OTH)

AF:

0.103

AC:

217

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

894

1789

2683

3578

4472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.0773

Hom.:

1263

Bravo

AF:

0.160

Asia WGS

AF:

0.171

AC:

595

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.37

(source)

DANN

Benign

0.66

PhyloP100

-2.1

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