chr21-40160403-A-G

Variant names:

• chr21-40160403-A-G
• rs2837468
• NM_001389.5:c.3018+6815T>C

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+6815T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,140 control chromosomes in the GnomAD database, including 5,146 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 0.26 (5146 hom., cov: 33)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.3018+6815T>C		intron_variant	Intron 16 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.3018+6815T>C		intron_variant	Intron 16 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.3515+6815T>C		intron_variant	Intron 16 of 32
DSCAM	XM_017028281.2	c.2310+6815T>C		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+6815T>C		intron_variant	Intron 16 of 32	1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.2274+6815T>C		intron_variant	Intron 12 of 28	1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.2523+6815T>C		intron_variant	Intron 13 of 29	5		ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38880 AN: 152022 Hom.: 5137 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.256 AC: 38920 AN: 152140 Hom.: 5146 Cov.: 33 AF XY: 0.257 AC XY: 19097 AN XY: 74382

African (AFR) AF: 0.218 AC: 9048 AN: 41504

American (AMR) AF: 0.253 AC: 3873 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3472

East Asian (EAS) AF: 0.362 AC: 1874 AN: 5172

South Asian (SAS) AF: 0.173 AC: 834 AN: 4826

European-Finnish (FIN) AF: 0.328 AC: 3469 AN: 10588

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18163 AN: 67974

Other (OTH) AF: 0.262 AC: 555 AN: 2116

Alfa AF: 0.262 Hom.: 8098

Bravo AF: 0.254

Asia WGS AF: 0.291 AC: 1010 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		1.9
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: rs2837468; hg19: chr21-41532330;