NM_024421.2:c.2130A>G

Variant names:

• chr18-31132676-T-C
• rs16961338
• NM_024421.2:c.2130A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024421.2(DSC1):​c.2130A>G​(p.Thr710Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,612,596 control chromosomes in the GnomAD database, including 315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (146 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (169 hom.)
• Consequence: DSC1 NM_024421.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.839
• Publications: 1 publications found

Genes affected

DSC1 (HGNC:3035): (desmocollin 1) The protein encoded by this gene is a calcium-dependent glycoprotein that is a member of the desmocollin subfamily of the cadherin superfamily. These desmosomal family members, along with the desmogleins, are found primarily in epithelial cells where they constitute the adhesive proteins of the desmosome cell-cell junction and are required for cell adhesion and desmosome formation. A subtype of IgA pemphigus, a life-threatening autoimmune disease, is characterized by the presence of autoantibodies that target the encoded protein. The desmosomal family members are arranged in two clusters on chromosome 18. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature protein. [provided by RefSeq, Nov 2015]

DSCAS (HGNC:51116): (DSC1/DSC2 antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 18-31132676-T-C is Benign according to our data. Variant chr18-31132676-T-C is described in ClinVar as Benign. ClinVar VariationId is 789105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.839 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024421.2. 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
	DSC1	NM_024421.2	MANE Select	c.2130A>G	p.Thr710Thr	synonymous	Exon 14 of 16	NP_077739.1	Q08554-1
	DSC1	NM_004948.3		c.2130A>G	p.Thr710Thr	synonymous	Exon 14 of 17	NP_004939.1	Q08554-2
	DSCAS	NR_110785.1		n.209-18123T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSC1	ENST00000257198.6	TSL:2 MANE Select	c.2130A>G	p.Thr710Thr	synonymous	Exon 14 of 16	ENSP00000257198.6	Q08554-1
	DSC1	ENST00000257197.7	TSL:1	c.2130A>G	p.Thr710Thr	synonymous	Exon 14 of 17	ENSP00000257197.3	Q08554-2
	DSCAS	ENST00000581836.2	TSL:4	n.225-18123T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3723 AN: 152122 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0867

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00628 AC: 1572 AN: 250292 AF XY: 0.00469

Gnomad AFR exome AF: 0.0881

Gnomad AMR exome AF: 0.00315

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00263

GnomAD4 exome AF: 0.00249 AC: 3636 AN: 1460356 Hom.: 169 Cov.: 30 AF XY: 0.00213 AC XY: 1550 AN XY: 726430

African (AFR) AF: 0.0914 AC: 3051 AN: 33374

American (AMR) AF: 0.00330 AC: 147 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39598

South Asian (SAS) AF: 0.000163 AC: 14 AN: 86118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53258

Middle Eastern (MID) AF: 0.00296 AC: 17 AN: 5752

European-Non Finnish (NFE) AF: 0.0000927 AC: 103 AN: 1111290

Other (OTH) AF: 0.00502 AC: 303 AN: 60300

GnomAD4 genome AF: 0.0245 AC: 3732 AN: 152240 Hom.: 146 Cov.: 32 AF XY: 0.0230 AC XY: 1713 AN XY: 74436

African (AFR) AF: 0.0866 AC: 3598 AN: 41530

American (AMR) AF: 0.00628 AC: 96 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68000

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00827 Hom.: 68

Bravo AF: 0.0285

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.0
DANN	Benign	0.75
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16961338; hg19: chr18-28712639;