rs6517590

Variant names:

• chr21-40324308-A-G
• rs6517590
• NM_001389.5:c.1784-11949T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-40324308-A-G
• chr21-40324308-A-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.1784-11949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,632 control chromosomes in the GnomAD database, including 30,780 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 0.63 (30780 hom., cov: 30)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.771 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.1784-11949T>C		intron	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.1784-11949T>C		intron	N/A	NP_001258463.1
	DSCAM	NR_073202.3		n.2281-11949T>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.1784-11949T>C		intron	N/A	ENSP00000383303.1
	DSCAM	ENST00000404019.2	TSL:1	c.1040-11949T>C		intron	N/A	ENSP00000385342.2
	DSCAM	ENST00000617870.4	TSL:5	c.1289-11949T>C		intron	N/A	ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95016 AN: 151514 Hom.: 30721 Cov.: 30

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.627 AC: 95134 AN: 151632 Hom.: 30780 Cov.: 30 AF XY: 0.635 AC XY: 47049 AN XY: 74072

African (AFR) AF: 0.778 AC: 32187 AN: 41346

American (AMR) AF: 0.663 AC: 10103 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1848 AN: 3466

East Asian (EAS) AF: 0.640 AC: 3296 AN: 5154

South Asian (SAS) AF: 0.669 AC: 3216 AN: 4804

European-Finnish (FIN) AF: 0.605 AC: 6314 AN: 10428

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36235 AN: 67892

Other (OTH) AF: 0.615 AC: 1297 AN: 2108

Alfa AF: 0.574 Hom.: 9879

Bravo AF: 0.638

Asia WGS AF: 0.654 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.44
PhyloP100		-0.36
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: rs6517590; hg19: chr21-41696235;