rs10522005

Positions:

• chrX-32543351-A-G
• chrX-32543351-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004006.3(DMD):​c.2168+1808T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 108,885 control chromosomes in the GnomAD database, including 5,477 homozygotes. There are 6,545 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.23 (5477 hom., 6545 hem., cov: 21)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-32543351-A-G is Benign according to our data. Variant chrX-32543351-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.2168+1808T>C		intron_variant		ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.2168+1808T>C		intron_variant		1	NM_004006.3	ENSP00000354923	P4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 25329 AN: 108853 Hom.: 5475 Cov.: 21 AF XY: 0.208 AC XY: 6530 AN XY: 31381

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.0394

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0224

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.0593

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.233 AC: 25354 AN: 108885 Hom.: 5477 Cov.: 21 AF XY: 0.208 AC XY: 6545 AN XY: 31423

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.0224

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.0530

Gnomad4 FIN AF: 0.0823

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.202

Alfa AF: 0.154 Hom.: 1105

Bravo AF: 0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs10522005; hg19: chrX-32561468;