rs2837588

Positions:

• chr21-40376132-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DSCAM	NM_001389.5	c.509-6887A>G		intron_variant		ENST00000400454.6
DSCAM	NM_001271534.3	c.509-6887A>G		intron_variant
DSCAM	NR_073202.3	n.1006-6887A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSCAM	ENST00000400454.6	c.509-6887A>G		intron_variant		1	NM_001389.5	P1

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

Gnomad4 AFR AF: 0.0548

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.0553

Gnomad4 NFE AF: 0.0530

Gnomad4 OTH AF: 0.0917

Alfa AF: 0.0723 Hom.: 708

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2837588; hg19: chr21-41748059;