X-31119880-G-T

Variant names:

• chrX-31119880-G-T
• rs72466523
• NM_004006.3:c.*2039C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004006.3(DMD):​c.*2039C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00649 in 111,776 control chromosomes in the GnomAD database, including 21 homozygotes. There are 306 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (21 hom., 306 hem., cov: 23)
  • Exomes 𝑓: 0.0034 (0 hom. 0 hem.)
• Consequence: DMD NM_004006.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.76
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Becker muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• dilated cardiomyopathy 3B

  Inheritance: XL Classification: DEFINITIVE Submitted by: Ambry Genetics
• Duchenne and Becker muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• Duchenne muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• progressive muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000297249 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant X-31119880-G-T is Benign according to our data. Variant chrX-31119880-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 368203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3	c.*2039C>A		3_prime_UTR_variant	Exon 79 of 79	ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.*2039C>A		3_prime_UTR_variant	Exon 79 of 79	1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.00641 AC: 714 AN: 111429 Hom.: 16 Cov.: 23

Gnomad AFR AF: 0.000848

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000863

Gnomad ASJ AF: 0.000379

Gnomad EAS AF: 0.0938

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.00685

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000226

Gnomad OTH AF: 0.00465

GnomAD4 exome AF: 0.00340 AC: 1 AN: 294 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 122

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00345 AC: 1 AN: 290

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1

Other (OTH) AF: 0.00 AC: 0 AN: 3

GnomAD4 genome AF: 0.00649 AC: 724 AN: 111482 Hom.: 21 Cov.: 23 AF XY: 0.00907 AC XY: 306 AN XY: 33744

African (AFR) AF: 0.000846 AC: 26 AN: 30740

American (AMR) AF: 0.000862 AC: 9 AN: 10439

Ashkenazi Jewish (ASJ) AF: 0.000379 AC: 1 AN: 2639

East Asian (EAS) AF: 0.0936 AC: 332 AN: 3548

South Asian (SAS) AF: 0.105 AC: 281 AN: 2681

European-Finnish (FIN) AF: 0.00685 AC: 41 AN: 5985

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000226 AC: 12 AN: 53025

Other (OTH) AF: 0.0144 AC: 22 AN: 1525

Alfa AF: 0.000356 Hom.: 3

Bravo AF: 0.00546

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated cardiomyopathy 3B Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.4
DANN	Benign	0.94
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72466523; hg19: chrX-31137997;