21-40331020-C-A

Variant names:

• chr21-40331020-C-A
• rs727333
• NM_001389.5:c.1783+7081G>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.1783+7081G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 152,046 control chromosomes in the GnomAD database, including 545 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 0.068 (545 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• 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 (AMR) allele frequency at 95% confidence interval = 0.166 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.1783+7081G>T		intron	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.1783+7081G>T		intron	N/A	NP_001258463.1
	DSCAM	NR_073202.3		n.2280+7081G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.1783+7081G>T		intron	N/A	ENSP00000383303.1
	DSCAM	ENST00000404019.2	TSL:1	c.1039+7081G>T		intron	N/A	ENSP00000385342.2
	DSCAM	ENST00000617870.4	TSL:5	c.1288+7081G>T		intron	N/A	ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10278 AN: 151926 Hom.: 539 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0906

Gnomad EAS AF: 0.0600

Gnomad SAS AF: 0.0370

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0773

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

GnomAD4 genome AF: 0.0677 AC: 10288 AN: 152046 Hom.: 545 Cov.: 32 AF XY: 0.0689 AC XY: 5121 AN XY: 74318

African (AFR) AF: 0.0150 AC: 621 AN: 41502

American (AMR) AF: 0.171 AC: 2613 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0906 AC: 314 AN: 3466

East Asian (EAS) AF: 0.0603 AC: 312 AN: 5174

South Asian (SAS) AF: 0.0364 AC: 175 AN: 4812

European-Finnish (FIN) AF: 0.0778 AC: 822 AN: 10560

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0755 AC: 5130 AN: 67960

Other (OTH) AF: 0.0760 AC: 160 AN: 2106

Alfa AF: 0.0751 Hom.: 1135

Bravo AF: 0.0755

Asia WGS AF: 0.0480 AC: 168 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	0.055
DANN	Benign	0.40
PhyloP100		-1.9
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: rs727333; hg19: chr21-41702947;