21-40157442-T-C

Variant names:

• chr21-40157442-T-C
• rs1554941
• NM_001389.5:c.3018+9776A>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.3018+9776A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,102 control chromosomes in the GnomAD database, including 32,204 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 0.64 (32204 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.3018+9776A>G		intron_variant	Intron 16 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.3018+9776A>G		intron_variant	Intron 16 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.3515+9776A>G		intron_variant	Intron 16 of 32
DSCAM	XM_017028281.2	c.2310+9776A>G		intron_variant	Intron 13 of 29		XP_016883770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.3018+9776A>G		intron_variant	Intron 16 of 32	1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.2274+9776A>G		intron_variant	Intron 12 of 28	1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.2523+9776A>G		intron_variant	Intron 13 of 29	5		ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97920 AN: 151984 Hom.: 32193 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.644 AC: 97970 AN: 152102 Hom.: 32204 Cov.: 32 AF XY: 0.647 AC XY: 48127 AN XY: 74342

African (AFR) AF: 0.520 AC: 21584 AN: 41484

American (AMR) AF: 0.674 AC: 10307 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2410 AN: 3470

East Asian (EAS) AF: 0.546 AC: 2805 AN: 5140

South Asian (SAS) AF: 0.743 AC: 3579 AN: 4814

European-Finnish (FIN) AF: 0.705 AC: 7475 AN: 10598

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47435 AN: 67988

Other (OTH) AF: 0.643 AC: 1356 AN: 2110

Alfa AF: 0.679 Hom.: 20252

Bravo AF: 0.639

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-0.64
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: rs1554941; hg19: chr21-41529369;