19-35511468-ACCACTGCTGCCGCCACTGCTGCCG-ACCACTGCTGCCGCCACTGCTGCCGCCACTGCTGCCG

Variant names:

• chr19-35511468-A-ACCACTGCTGCCG
• rs760401945
• NM_033317.5:c.849_860dupCGGCAGCAGTGG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BS1 BS2

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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033317.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMKN	NM_033317.5	MANE Select	c.849_860dupCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 16	NP_201574.4
	DMKN	NM_001190348.2		c.849_860dupCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 13	NP_001177277.1	Q6E0U4-6
	DMKN	NM_001126057.3		c.849_860dupCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 11	NP_001119529.2	Q6E0U4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMKN	ENST00000339686.8	TSL:1 MANE Select	c.849_860dupCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 16	ENSP00000342012.3	Q6E0U4-1
	DMKN	ENST00000447113.6	TSL:1	c.849_860dupCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 13	ENSP00000394908.2	Q6E0U4-6
	DMKN	ENST00000424570.6	TSL:1	c.849_860dupCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 11	ENSP00000388404.2	Q6E0U4-5

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 1224 AN: 84140 Hom.: 10 Cov.: 22

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.: 53 Cov.: 29 AF XY: 0.00968 AC XY: 4836 AN XY: 499544

African (AFR) AF: 0.0171 AC: 341 AN: 19910

American (AMR) AF: 0.00927 AC: 164 AN: 17686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17456

East Asian (EAS) AF: 0.00235 AC: 37 AN: 15720

South Asian (SAS) AF: 0.0264 AC: 1340 AN: 50744

European-Finnish (FIN) AF: 0.00859 AC: 267 AN: 31072

Middle Eastern (MID) AF: 0.0107 AC: 31 AN: 2884

European-Non Finnish (NFE) AF: 0.00849 AC: 6912 AN: 814378

Other (OTH) AF: 0.00826 AC: 336 AN: 40692

GnomAD4 genome AF: 0.0146 AC: 1226 AN: 84156 Hom.: 10 Cov.: 22 AF XY: 0.0150 AC XY: 614 AN XY: 40922

African (AFR) AF: 0.0295 AC: 490 AN: 16626

American (AMR) AF: 0.0181 AC: 130 AN: 7172

Ashkenazi Jewish (ASJ) AF: 0.000443 AC: 1 AN: 2256

East Asian (EAS) AF: 0.00267 AC: 5 AN: 1874

South Asian (SAS) AF: 0.0312 AC: 80 AN: 2566

European-Finnish (FIN) AF: 0.0122 AC: 80 AN: 6554

Middle Eastern (MID) AF: 0.0206 AC: 4 AN: 194

European-Non Finnish (NFE) AF: 0.00950 AC: 428 AN: 45046

Other (OTH) AF: 0.00672 AC: 8 AN: 1190

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=89/11	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs760401945; hg19: chr19-36002370; COSMIC: COSV104413887; COSMIC: COSV104413887;