rs447940

Variant names:

• chr21-40224373-T-C
• rs447940
• NM_001389.5:c.2357-35135A>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.2357-35135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,130 control chromosomes in the GnomAD database, including 25,234 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 0.55 (25234 hom., cov: 33)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.2357-35135A>G		intron_variant	Intron 11 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.2357-35135A>G		intron_variant	Intron 11 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.2854-35135A>G		intron_variant	Intron 11 of 32
DSCAM	XM_017028281.2	c.1649-35135A>G		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.2357-35135A>G		intron_variant	Intron 11 of 32	1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.1613-35135A>G		intron_variant	Intron 7 of 28	1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.1862-35135A>G		intron_variant	Intron 8 of 29	5		ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84130 AN: 152012 Hom.: 25197 Cov.: 33

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.554 AC: 84230 AN: 152130 Hom.: 25234 Cov.: 33 AF XY: 0.551 AC XY: 40943 AN XY: 74368

African (AFR) AF: 0.793 AC: 32909 AN: 41520

American (AMR) AF: 0.442 AC: 6758 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1477 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1554 AN: 5182

South Asian (SAS) AF: 0.529 AC: 2551 AN: 4818

European-Finnish (FIN) AF: 0.519 AC: 5487 AN: 10578

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.468 AC: 31792 AN: 67966

Other (OTH) AF: 0.533 AC: 1123 AN: 2106

Alfa AF: 0.520 Hom.: 4269

Bravo AF: 0.557

Asia WGS AF: 0.406 AC: 1415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.68
PhyloP100		-1.1
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: rs447940; hg19: chr21-41596300;