Genetic Variant DMD:c.*1783A>G (chrX-31120136-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004006.3(DMD):c.*1783A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 111,003 control chromosomes in the GnomAD database, including 68 homozygotes. There are 859 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 68 hom., 859 hem., cov: 22)

Exomes 𝑓: 0.0033 ( 0 hom. 0 hem. )

Consequence

DMD
NM_004006.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.385

Variant links:

Genes affected

DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]

DMD links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant X-31120136-T-C is Benign according to our data. Variant chrX-31120136-T-C is described in ClinVar as [Benign]. Clinvar id is 368205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-31120136-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3 link	c.*1783A>G		3_prime_UTR_variant	Exon 79 of 79	ENST00000357033.9	NP_003997.2	P11532

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033 link	c.*1783A>G		3_prime_UTR_variant	Exon 79 of 79	1	NM_004006.3	ENSP00000354923.3		A0A075B6G3

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

2782

AN:

110650

Hom.:

Cov.:

AF XY:

0.0255

AC XY:

853

AN XY:

33492

show subpopulations

Gnomad AFR

AF:

0.0609

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00669

Gnomad ASJ

AF:

0.000384

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.00732

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000646

Gnomad OTH

AF:

0.0154

GnomAD4 exome

AF:

0.00333

AC:

AN:

300

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

128

show subpopulations

Gnomad4 FIN exome

AF:

0.00338

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0252

AC:

2793

AN:

110703

Hom.:

Cov.:

AF XY:

0.0256

AC XY:

859

AN XY:

33555

show subpopulations

Gnomad4 AFR

AF:

0.0608

Gnomad4 AMR

AF:

0.00668

Gnomad4 ASJ

AF:

0.000384

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.00732

Gnomad4 NFE

AF:

0.000627

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.0137

Hom.:

128

Bravo

AF:

0.0268

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dilated cardiomyopathy 3B

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.4

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over