Genetic Variant DSP:c.-15C>T (chr6-7541901-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004415.4(DSP):c.-15C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,602,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

DSP
NM_004415.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15

Publications

0 publications found

Variant links:

Genes affected

DSP (HGNC:3052): (desmoplakin) This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DSP links:

DSP-AS1 (HGNC:56039): (DSP antisense RNA 1)

DSP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004415.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DSP	NM_004415.4	MANE Select	c.-15C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 24	NP_004406.2	P15924-1
DSP	NM_004415.4	MANE Select	c.-15C>T	5_prime_UTR	Exon 1 of 24	NP_004406.2	P15924-1
DSP	NM_001319034.2		c.-15C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 24	NP_001305963.1	P15924-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DSP	ENST00000379802.8	TSL:1 MANE Select	c.-15C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 24	ENSP00000369129.3	P15924-1
DSP	ENST00000418664.3	TSL:1	c.-15C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 24	ENSP00000396591.2	P15924-2
DSP	ENST00000379802.8	TSL:1 MANE Select	c.-15C>T	5_prime_UTR	Exon 1 of 24	ENSP00000369129.3	P15924-1

Frequencies

GnomAD3 genomes

AF:

0.00000677

AC:

AN:

147782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000918

AC:

AN:

217892

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000630

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1454728

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723092

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33366

American (AMR)

AF:

0.0000452

AC:

AN:

44246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26010

East Asian (EAS)

AF:

0.00

AC:

AN:

39468

South Asian (SAS)

AF:

0.00

AC:

AN:

85154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50920

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5534

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1109978

Other (OTH)

AF:

0.00

AC:

AN:

60052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000677

AC:

AN:

147782

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39734

American (AMR)

AF:

0.00

AC:

AN:

14598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

4826

South Asian (SAS)

AF:

0.00

AC:

AN:

4730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66844

Other (OTH)

AF:

0.00

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.2

(source)

DANN

Benign

0.96

PhyloP100

-1.1

PromoterAI

-0.044

Neutral

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over