NM_001389.5:c.509-6887A>G

Variant names:

• chr21-40376132-T-C
• rs2837588
• NM_001389.5:c.509-6887A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001389.5(DSCAM):​c.509-6887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 152,192 control chromosomes in the GnomAD database, including 793 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 0.078 (793 hom., cov: 33)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.509-6887A>G		intron_variant	Intron 3 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.509-6887A>G		intron_variant	Intron 3 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.1006-6887A>G		intron_variant	Intron 3 of 32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.509-6887A>G		intron_variant	Intron 3 of 32	1	NM_001389.5	ENSP00000383303.1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11816 AN: 152074 Hom.: 784 Cov.: 33

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0324

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0893

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

GnomAD4 genome AF: 0.0778 AC: 11848 AN: 152192 Hom.: 793 Cov.: 33 AF XY: 0.0818 AC XY: 6088 AN XY: 74416

African (AFR) AF: 0.0548 AC: 2275 AN: 41540

American (AMR) AF: 0.230 AC: 3515 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1171 AN: 5172

South Asian (SAS) AF: 0.0324 AC: 156 AN: 4818

European-Finnish (FIN) AF: 0.0553 AC: 586 AN: 10594

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0530 AC: 3605 AN: 68008

Other (OTH) AF: 0.0917 AC: 194 AN: 2116

Alfa AF: 0.0747 Hom.: 966

Bravo AF: 0.0954

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		0.53
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: rs2837588; hg19: chr21-41748059;