chr21-40151580-A-G

Variant names:

• chr21-40151580-A-G
• rs8130732
• NM_001389.5:c.3019-6849T>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.3019-6849T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,132 control chromosomes in the GnomAD database, including 42,968 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 0.75 (42968 hom., cov: 33)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 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.3019-6849T>C		intron	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.3019-6849T>C		intron	N/A	NP_001258463.1
	DSCAM	NR_073202.3		n.3516-6849T>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.3019-6849T>C		intron	N/A	ENSP00000383303.1
	DSCAM	ENST00000404019.2	TSL:1	c.2275-6849T>C		intron	N/A	ENSP00000385342.2
	DSCAM	ENST00000617870.4	TSL:5	c.2524-6849T>C		intron	N/A	ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113991 AN: 152014 Hom.: 42924 Cov.: 33

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.750 AC: 114091 AN: 152132 Hom.: 42968 Cov.: 33 AF XY: 0.751 AC XY: 55855 AN XY: 74378

African (AFR) AF: 0.733 AC: 30413 AN: 41496

American (AMR) AF: 0.722 AC: 11025 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2626 AN: 3470

East Asian (EAS) AF: 0.724 AC: 3748 AN: 5180

South Asian (SAS) AF: 0.831 AC: 4004 AN: 4820

European-Finnish (FIN) AF: 0.768 AC: 8126 AN: 10574

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51550 AN: 68006

Other (OTH) AF: 0.742 AC: 1565 AN: 2110

Alfa AF: 0.758 Hom.: 22531

Bravo AF: 0.747

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.50
PhyloP100		-0.13
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: rs8130732; hg19: chr21-41523507;