chr21-40152704-T-C

Variant names:

• chr21-40152704-T-C
• rs11911749
• NM_001389.5:c.3019-7973A>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.3019-7973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,282 control chromosomes in the GnomAD database, including 46,069 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 0.78 (46069 hom., cov: 36)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.3019-7973A>G		intron_variant	Intron 16 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.3019-7973A>G		intron_variant	Intron 16 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.3516-7973A>G		intron_variant	Intron 16 of 32
DSCAM	XM_017028281.2	c.2311-7973A>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.3019-7973A>G		intron_variant	Intron 16 of 32	1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.2275-7973A>G		intron_variant	Intron 12 of 28	1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.2524-7973A>G		intron_variant	Intron 13 of 29	5		ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118139 AN: 152164 Hom.: 46009 Cov.: 36

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.777 AC: 118263 AN: 152282 Hom.: 46069 Cov.: 36 AF XY: 0.777 AC XY: 57846 AN XY: 74440

African (AFR) AF: 0.815 AC: 33878 AN: 41566

American (AMR) AF: 0.731 AC: 11183 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2652 AN: 3472

East Asian (EAS) AF: 0.731 AC: 3783 AN: 5172

South Asian (SAS) AF: 0.846 AC: 4085 AN: 4826

European-Finnish (FIN) AF: 0.768 AC: 8144 AN: 10598

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.763 AC: 51893 AN: 68026

Other (OTH) AF: 0.756 AC: 1600 AN: 2116

Alfa AF: 0.767 Hom.: 16546

Bravo AF: 0.775

Asia WGS AF: 0.816 AC: 2833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		-1.3
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: rs11911749; hg19: chr21-41524631;