chr21-40662426-G-A

Variant names:

• chr21-40662426-G-A
• rs2837770
• NM_001389.5:c.508+30384C>T

Variant summary

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

The NM_001389.5(DSCAM):​c.508+30384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,950 control chromosomes in the GnomAD database, including 10,505 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 0.35 (10505 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.508+30384C>T		intron_variant	Intron 3 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.508+30384C>T		intron_variant	Intron 3 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.1005+30384C>T		intron_variant	Intron 3 of 32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.508+30384C>T		intron_variant	Intron 3 of 32	1	NM_001389.5	ENSP00000383303.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52491 AN: 151832 Hom.: 10495 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.346 AC: 52528 AN: 151950 Hom.: 10505 Cov.: 32 AF XY: 0.348 AC XY: 25818 AN XY: 74244

African (AFR) AF: 0.151 AC: 6261 AN: 41448

American (AMR) AF: 0.290 AC: 4431 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1479 AN: 3466

East Asian (EAS) AF: 0.403 AC: 2082 AN: 5166

South Asian (SAS) AF: 0.344 AC: 1655 AN: 4806

European-Finnish (FIN) AF: 0.461 AC: 4851 AN: 10514

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30488 AN: 67964

Other (OTH) AF: 0.360 AC: 761 AN: 2112

Alfa AF: 0.371 Hom.: 2011

Bravo AF: 0.323

Asia WGS AF: 0.354 AC: 1229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.51
PhyloP100		-0.45
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: rs2837770; hg19: chr21-42034352;