chr21-40107771-C-T

Variant names:

• chr21-40107771-C-T
• rs451518
• NM_001389.5:c.3697-13897G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001389.5(DSCAM):​c.3697-13897G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,126 control chromosomes in the GnomAD database, including 60,585 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 0.89 (60585 hom., cov: 30)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.3697-13897G>A		intron_variant	Intron 20 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.3697-13897G>A		intron_variant	Intron 20 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.4194-13897G>A		intron_variant	Intron 20 of 32
DSCAM	XM_017028281.2	c.2989-13897G>A		intron_variant	Intron 17 of 29		XP_016883770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.3697-13897G>A		intron_variant	Intron 20 of 32	1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.2953-13897G>A		intron_variant	Intron 16 of 28	1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.3202-13897G>A		intron_variant	Intron 17 of 29	5		ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135391 AN: 152008 Hom.: 60532 Cov.: 30

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.993

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.891 AC: 135502 AN: 152126 Hom.: 60585 Cov.: 30 AF XY: 0.893 AC XY: 66376 AN XY: 74368

African (AFR) AF: 0.808 AC: 33495 AN: 41450

American (AMR) AF: 0.927 AC: 14181 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 3398 AN: 3468

East Asian (EAS) AF: 0.911 AC: 4710 AN: 5172

South Asian (SAS) AF: 0.934 AC: 4505 AN: 4824

European-Finnish (FIN) AF: 0.939 AC: 9937 AN: 10588

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62148 AN: 68010

Other (OTH) AF: 0.919 AC: 1941 AN: 2112

Alfa AF: 0.906 Hom.: 77524

Bravo AF: 0.889

Asia WGS AF: 0.933 AC: 3245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.30
PhyloP100		-0.70
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: rs451518; hg19: chr21-41479698;