21-40157442-T-C

Position:

• chr21-40157442-T-C

Variant summary

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

The NM_001389.5(DSCAM):​c.3018+9776A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,102 control chromosomes in the GnomAD database, including 32,204 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 0.64 (32204 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.3018+9776A>G		intron_variant		ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.3018+9776A>G		intron_variant			NP_001258463.1
DSCAM	XM_017028281.2	c.2310+9776A>G		intron_variant			XP_016883770.1
DSCAM	NR_073202.3	n.3515+9776A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.3018+9776A>G		intron_variant		1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.2274+9776A>G		intron_variant		1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.2523+9776A>G		intron_variant		5		ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97920 AN: 151984 Hom.: 32193 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.644 AC: 97970 AN: 152102 Hom.: 32204 Cov.: 32 AF XY: 0.647 AC XY: 48127 AN XY: 74342

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.643

Alfa AF: 0.679 Hom.: 18277

Bravo AF: 0.639

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.76

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: rs1554941; hg19: chr21-41529369;