chr21-40233218-C-T

Variant names:

• chr21-40233218-C-T
• rs2837524
• NM_001389.5:c.2356+42879G>A

Variant summary

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

The NM_001389.5(DSCAM):​c.2356+42879G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,764 control chromosomes in the GnomAD database, including 16,916 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 0.46 (16916 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.2356+42879G>A		intron_variant	Intron 11 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.2356+42879G>A		intron_variant	Intron 11 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.2853+42879G>A		intron_variant	Intron 11 of 32
DSCAM	XM_017028281.2	c.1648+42879G>A		intron_variant	Intron 8 of 29		XP_016883770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.2356+42879G>A		intron_variant	Intron 11 of 32	1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.1612+42879G>A		intron_variant	Intron 7 of 28	1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.1861+42879G>A		intron_variant	Intron 8 of 29	5		ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70378 AN: 151650 Hom.: 16894 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.464 AC: 70453 AN: 151764 Hom.: 16916 Cov.: 32 AF XY: 0.462 AC XY: 34269 AN XY: 74154

African (AFR) AF: 0.589 AC: 24399 AN: 41390

American (AMR) AF: 0.387 AC: 5901 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1263 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1385 AN: 5170

South Asian (SAS) AF: 0.419 AC: 2016 AN: 4808

European-Finnish (FIN) AF: 0.470 AC: 4908 AN: 10450

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

European-Non Finnish (NFE) AF: 0.429 AC: 29160 AN: 67924

Other (OTH) AF: 0.445 AC: 936 AN: 2102

Alfa AF: 0.411 Hom.: 5315

Bravo AF: 0.462

Asia WGS AF: 0.333 AC: 1160 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.53
PhyloP100		-0.15
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: rs2837524; hg19: chr21-41605145;