rs2205081

Positions:

• chr21-40337067-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001389.5(DSCAM):​c.1783+1034T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,040 control chromosomes in the GnomAD database, including 16,917 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 0.46 (16917 hom., cov: 33)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSCAM	NM_001389.5	c.1783+1034T>C		intron_variant		ENST00000400454.6
DSCAM	NM_001271534.3	c.1783+1034T>C		intron_variant
DSCAM	XM_017028281.2	c.1075+1034T>C		intron_variant
DSCAM	NR_073202.3	n.2280+1034T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSCAM	ENST00000400454.6	c.1783+1034T>C		intron_variant		1	NM_001389.5	P1
DSCAM	ENST00000404019.2	c.1039+1034T>C		intron_variant		1
DSCAM	ENST00000617870.4	c.1288+1034T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70595 AN: 151922 Hom.: 16918 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.464 AC: 70611 AN: 152040 Hom.: 16917 Cov.: 33 AF XY: 0.467 AC XY: 34699 AN XY: 74312

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.429

Alfa AF: 0.480 Hom.: 23226

Bravo AF: 0.459

Asia WGS AF: 0.587 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.44
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs2205081; hg19: chr21-41708994;