NM_001389.5:c.43+1590G>A

Variant names:

• chr21-40845029-C-T
• rs2837857
• NM_001389.5:c.43+1590G>A

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+1590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,964 control chromosomes in the GnomAD database, including 9,067 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 0.30 (9067 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.43+1590G>A		intron_variant	Intron 1 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.43+1590G>A		intron_variant	Intron 1 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.540+1590G>A		intron_variant	Intron 1 of 32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.43+1590G>A		intron_variant	Intron 1 of 32	1	NM_001389.5	ENSP00000383303.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46209 AN: 151846 Hom.: 9054 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.304 AC: 46267 AN: 151964 Hom.: 9067 Cov.: 32 AF XY: 0.307 AC XY: 22788 AN XY: 74272

African (AFR) AF: 0.557 AC: 23039 AN: 41390

American (AMR) AF: 0.280 AC: 4267 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3466

East Asian (EAS) AF: 0.279 AC: 1441 AN: 5164

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4812

European-Finnish (FIN) AF: 0.258 AC: 2730 AN: 10562

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12391 AN: 67990

Other (OTH) AF: 0.282 AC: 596 AN: 2110

Alfa AF: 0.226 Hom.: 5776

Bravo AF: 0.315

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.76
DANN	Benign	0.65
PhyloP100		-0.69
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: rs2837857; hg19: chr21-42216955;