Genetic Variant DYM:c.2026-9396G>A (chr18-49053600-C-T) – 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.2026-9396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,978 control chromosomes in the GnomAD database, including 24,641 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 0.56 ( 24641 hom., cov: 32)

Consequence

DYM
NM_001353214.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.423

Publications

12 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=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 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.2026-9396G>A	intron	N/A	NP_001340143.1	A0A6Q8PF81
DYM	NM_001374428.1		c.2026-9396G>A	intron	N/A	NP_001361357.1	A0A6Q8PF81
DYM	NM_001353212.3		c.2023-9396G>A	intron	N/A	NP_001340141.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYM	ENST00000675505.1	MANE Select	c.2026-9396G>A	intron	N/A	ENSP00000501694.1	A0A6Q8PF81
DYM	ENST00000269445.10	TSL:1	c.1861-9396G>A	intron	N/A	ENSP00000269445.6	Q7RTS9-1
DYM	ENST00000919568.1		c.1861-9396G>A	intron	N/A	ENSP00000589627.1

Frequencies

GnomAD3 genomes

AF:

0.564

AC:

85611

AN:

151860

Hom.:

24619

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.606

Gnomad OTH

AF:

0.604

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

GnomAD4 genome

AF:

0.564

AC:

85683

AN:

151978

Hom.:

24641

Cov.:

AF XY:

0.565

AC XY:

41942

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.479

AC:

19837

AN:

41412

American (AMR)

AF:

0.667

AC:

10194

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1952

AN:

3466

East Asian (EAS)

AF:

0.326

AC:

1683

AN:

5164

South Asian (SAS)

AF:

0.512

AC:

2464

AN:

4814

European-Finnish (FIN)

AF:

0.612

AC:

6464

AN:

10564

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.606

AC:

41218

AN:

67966

Other (OTH)

AF:

0.597

AC:

1262

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1885

3771

5656

7542

9427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.590

Hom.:

70033

Bravo

AF:

0.564

Asia WGS

AF:

0.425

AC:

1482

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.5

(source)

DANN

Benign

0.53

PhyloP100

-0.42

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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