rs12152040

Variant names:

• chr21-40697142-T-C
• rs12152040
• NM_001389.5:c.362-4186A>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.362-4186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,132 control chromosomes in the GnomAD database, including 1,454 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 0.13 (1454 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.362-4186A>G		intron_variant	Intron 2 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.362-4186A>G		intron_variant	Intron 2 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.859-4186A>G		intron_variant	Intron 2 of 32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.362-4186A>G		intron_variant	Intron 2 of 32	1	NM_001389.5	ENSP00000383303.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20377 AN: 152014 Hom.: 1450 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.134 AC: 20405 AN: 152132 Hom.: 1454 Cov.: 32 AF XY: 0.135 AC XY: 10054 AN XY: 74366

African (AFR) AF: 0.151 AC: 6267 AN: 41488

American (AMR) AF: 0.186 AC: 2842 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3470

East Asian (EAS) AF: 0.0713 AC: 369 AN: 5172

South Asian (SAS) AF: 0.159 AC: 764 AN: 4808

European-Finnish (FIN) AF: 0.142 AC: 1508 AN: 10584

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.112 AC: 7643 AN: 68014

Other (OTH) AF: 0.149 AC: 315 AN: 2108

Alfa AF: 0.125 Hom.: 3851

Bravo AF: 0.139

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.65
PhyloP100		-0.39
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: rs12152040; hg19: chr21-42069068;