21-40803034-A-G

Variant names:

• chr21-40803034-A-G
• rs2837828
• NM_001389.5:c.43+43585T>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.43+43585T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,026 control chromosomes in the GnomAD database, including 17,239 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 0.45 (17239 hom., cov: 31)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	NM_001389.5	MANE Select	c.43+43585T>C		intron	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.43+43585T>C		intron	N/A	NP_001258463.1
	DSCAM	NR_073202.3		n.540+43585T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.43+43585T>C		intron	N/A	ENSP00000383303.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68301 AN: 151906 Hom.: 17227 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.449 AC: 68327 AN: 152026 Hom.: 17239 Cov.: 31 AF XY: 0.452 AC XY: 33558 AN XY: 74294

African (AFR) AF: 0.212 AC: 8795 AN: 41452

American (AMR) AF: 0.505 AC: 7725 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1935 AN: 3466

East Asian (EAS) AF: 0.380 AC: 1962 AN: 5158

South Asian (SAS) AF: 0.642 AC: 3091 AN: 4816

European-Finnish (FIN) AF: 0.485 AC: 5124 AN: 10566

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38048 AN: 67962

Other (OTH) AF: 0.462 AC: 975 AN: 2110

Alfa AF: 0.509 Hom.: 28677

Bravo AF: 0.437

Asia WGS AF: 0.507 AC: 1762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.39
DANN	Benign	0.75
PhyloP100		-0.93
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: rs2837828; hg19: chr21-42174960;