chr21-40514656-T-C

Variant names:

• chr21-40514656-T-C
• rs9980603
• NM_001389.5:c.509-145411A>G

Variant summary

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

The NM_001389.5(DSCAM):​c.509-145411A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,070 control chromosomes in the GnomAD database, including 12,041 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 0.40 (12041 hom., cov: 33)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.670
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 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.509-145411A>G		intron	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.509-145411A>G		intron	N/A	NP_001258463.1
	DSCAM	NR_073202.3		n.1006-145411A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.509-145411A>G		intron	N/A	ENSP00000383303.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60053 AN: 151952 Hom.: 12028 Cov.: 33

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.395 AC: 60086 AN: 152070 Hom.: 12041 Cov.: 33 AF XY: 0.390 AC XY: 29027 AN XY: 74336

African (AFR) AF: 0.408 AC: 16903 AN: 41474

American (AMR) AF: 0.351 AC: 5358 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1182 AN: 5184

South Asian (SAS) AF: 0.317 AC: 1529 AN: 4822

European-Finnish (FIN) AF: 0.428 AC: 4523 AN: 10570

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27930 AN: 67962

Other (OTH) AF: 0.378 AC: 799 AN: 2114

Alfa AF: 0.406 Hom.: 21076

Bravo AF: 0.393

Asia WGS AF: 0.247 AC: 860 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	5.4
DANN	Benign	0.66
PhyloP100		0.67
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: rs9980603; hg19: chr21-41886583;