ENST00000288447.9:c.7+102465G>C

Variant names:

• chrX-33236794-C-G
• rs10522021
• ENST00000288447.9:c.7+102465G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000288447.9(DMD):​c.7+102465G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 111,069 control chromosomes in the GnomAD database, including 1,223 homozygotes. There are 3,746 hemizygotes in GnomAD. 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 0.12 (1223 hom., 3746 hem., cov: 21)
• Consequence: DMD ENST00000288447.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_000109.4	c.7+102465G>C		intron_variant	Intron 1 of 78		NP_000100.3
DMD	XM_006724469.4	c.7+102465G>C		intron_variant	Intron 1 of 77		XP_006724532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000288447.9	c.7+102465G>C		intron_variant	Intron 1 of 17	1		ENSP00000288447.4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 13449 AN: 111020 Hom.: 1220 Cov.: 21

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0750

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0644

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.121 AC: 13475 AN: 111069 Hom.: 1223 Cov.: 21 AF XY: 0.112 AC XY: 3746 AN XY: 33325

African (AFR) AF: 0.318 AC: 9651 AN: 30396

American (AMR) AF: 0.0649 AC: 681 AN: 10485

Ashkenazi Jewish (ASJ) AF: 0.0644 AC: 170 AN: 2639

East Asian (EAS) AF: 0.0208 AC: 73 AN: 3508

South Asian (SAS) AF: 0.0965 AC: 253 AN: 2622

European-Finnish (FIN) AF: 0.0183 AC: 110 AN: 6009

Middle Eastern (MID) AF: 0.122 AC: 26 AN: 213

European-Non Finnish (NFE) AF: 0.0433 AC: 2298 AN: 53019

Other (OTH) AF: 0.108 AC: 162 AN: 1498

Alfa AF: 0.0871 Hom.: 476

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.46
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10522021; hg19: chrX-33254911;