21-40043117-T-C

Variant names:

• chr21-40043117-T-C
• rs9981861
• NM_001389.5:c.5384-444A>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.5384-444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,018 control chromosomes in the GnomAD database, including 13,747 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 0.41 (13747 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• Publications: 22 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 (NFE) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.5384-444A>G		intron_variant	Intron 31 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.5384-444A>G		intron_variant	Intron 31 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.5690-444A>G		intron_variant	Intron 31 of 32
DSCAM	XM_017028281.2	c.4676-444A>G		intron_variant	Intron 28 of 29		XP_016883770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.5384-444A>G		intron_variant	Intron 31 of 32	1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.4640-444A>G		intron_variant	Intron 27 of 28	1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.4889-444A>G		intron_variant	Intron 28 of 29	5		ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62938 AN: 151900 Hom.: 13748 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.414 AC: 62962 AN: 152018 Hom.: 13747 Cov.: 32 AF XY: 0.416 AC XY: 30923 AN XY: 74302

African (AFR) AF: 0.312 AC: 12946 AN: 41468

American (AMR) AF: 0.381 AC: 5822 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3468

East Asian (EAS) AF: 0.189 AC: 977 AN: 5168

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4816

European-Finnish (FIN) AF: 0.553 AC: 5850 AN: 10570

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32514 AN: 67960

Other (OTH) AF: 0.432 AC: 906 AN: 2098

Alfa AF: 0.450 Hom.: 61845

Bravo AF: 0.391

Asia WGS AF: 0.300 AC: 1045 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	2.1
DANN	Benign	0.32
PhyloP100		-0.26
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: rs9981861; hg19: chr21-41415044;