rs2205081

Variant names:

• chr21-40337067-A-G
• rs2205081
• NM_001389.5:c.1783+1034T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001389.5(DSCAM):​c.1783+1034T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,040 control chromosomes in the GnomAD database, including 16,917 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16917 hom., cov: 33)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 2 publications found

Genes affected

DSCAM (HGNC:3039): (DS cell adhesion molecule) This gene is a member of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAMs), and is involved in human central and peripheral nervous system development. This gene is a candidate for Down syndrome and congenital heart disease (DSCHD). A gene encoding a similar Ig-CAM protein is located on chromosome 11. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

DSCAM Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389.5. 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
	DSCAM	NM_001389.5	MANE Select	c.1783+1034T>C		intron	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.1783+1034T>C		intron	N/A	NP_001258463.1
	DSCAM	NR_073202.3		n.2280+1034T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.1783+1034T>C		intron	N/A	ENSP00000383303.1	O60469-1
	DSCAM	ENST00000404019.2	TSL:1	c.1039+1034T>C		intron	N/A	ENSP00000385342.2	Q8WY19
	DSCAM	ENST00000617870.4	TSL:5	c.1288+1034T>C		intron	N/A	ENSP00000478698.1	A0A087WUI7

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70595 AN: 151922 Hom.: 16918 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.464 AC: 70611 AN: 152040 Hom.: 16917 Cov.: 33 AF XY: 0.467 AC XY: 34699 AN XY: 74312

African (AFR) AF: 0.387 AC: 16066 AN: 41468

American (AMR) AF: 0.539 AC: 8227 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1382 AN: 3466

East Asian (EAS) AF: 0.498 AC: 2562 AN: 5146

South Asian (SAS) AF: 0.650 AC: 3132 AN: 4816

European-Finnish (FIN) AF: 0.455 AC: 4812 AN: 10566

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 33001 AN: 67988

Other (OTH) AF: 0.429 AC: 907 AN: 2112

Alfa AF: 0.477 Hom.: 52247

Bravo AF: 0.459

Asia WGS AF: 0.587 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.44
DANN	Benign	0.46
PhyloP100		-1.6
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: rs2205081; hg19: chr21-41708994;