Variant 19-35511468-A-ACCACTGCTGCCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The NM_033317.5(DMKN):c.849_860dupCGGCAGCAGTGG(p.Gly287_Gly288insGlySerSerGly) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 84,156 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 10 hom., cov: 22)

Exomes 𝑓: 0.0093 ( 53 hom. )

Failed GnomAD Quality Control

Consequence

DMKN
NM_033317.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.49

Variant links:

Genes affected

DMKN (HGNC:25063): (dermokine) This gene is upregulated in inflammatory diseases, and it was first observed as expressed in the differentiated layers of skin. The most interesting aspect of this gene is the differential use of promoters and terminators to generate isoforms with unique cellular distributions and domain components. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]

DMKN links:

DMKN (HGNC:):

DMKN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_033317.5.

BP6

Variant 19-35511468-A-ACCACTGCTGCCG is Benign according to our data. Variant chr19-35511468-A-ACCACTGCTGCCG is described in ClinVar as [Benign]. Clinvar id is 719578.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0146 (1226/84156) while in subpopulation SAS AF= 0.0312 (80/2566). AF 95% confidence interval is 0.0273. There are 10 homozygotes in gnomad4. There are 614 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMKN	NM_033317.5 linkuse as main transcript	c.849_860dupCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGly	disruptive_inframe_insertion	5/16	ENST00000339686.8	NP_201574.4	Q6E0U4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMKN	ENST00000339686.8 linkuse as main transcript	c.849_860dupCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGly	disruptive_inframe_insertion	5/16	1	NM_033317.5	ENSP00000342012.3		Q6E0U4-1

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

1224

AN:

84140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.000443

Gnomad EAS

AF:

0.00213

Gnomad SAS

AF:

0.0310

Gnomad FIN

AF:

0.0122

Gnomad MID

AF:

0.0192

Gnomad NFE

AF:

0.00950

Gnomad OTH

AF:

0.00685

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00933

AC:

9428

AN:

1010542

Hom.:

Cov.:

AF XY:

0.00968

AC XY:

4836

AN XY:

499544

show subpopulations

Gnomad4 AFR exome

AF:

0.0171

Gnomad4 AMR exome

AF:

0.00927

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00235

Gnomad4 SAS exome

AF:

0.0264

Gnomad4 FIN exome

AF:

0.00859

Gnomad4 NFE exome

AF:

0.00849

Gnomad4 OTH exome

AF:

0.00826

GnomAD4 genome

AF:

0.0146

AC:

1226

AN:

84156

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

614

AN XY:

40922

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.000443

Gnomad4 EAS

AF:

0.00267

Gnomad4 SAS

AF:

0.0312

Gnomad4 FIN

AF:

0.0122

Gnomad4 NFE

AF:

0.00950

Gnomad4 OTH

AF:

0.00672

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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