chr21-40043117-T-C

Position:

• chr21-40043117-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.5384-444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,018 control chromosomes in the GnomAD database, including 13,747 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 0.41 (13747 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.5384-444A>G		intron_variant		ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.5384-444A>G		intron_variant			NP_001258463.1
DSCAM	XM_017028281.2	c.4676-444A>G		intron_variant			XP_016883770.1
DSCAM	NR_073202.3	n.5690-444A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.5384-444A>G		intron_variant		1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.4640-444A>G		intron_variant		1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.4889-444A>G		intron_variant		5		ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62938 AN: 151900 Hom.: 13748 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.414 AC: 62962 AN: 152018 Hom.: 13747 Cov.: 32 AF XY: 0.416 AC XY: 30923 AN XY: 74302

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.432

Alfa AF: 0.457 Hom.: 28125

Bravo AF: 0.391

Asia WGS AF: 0.300 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.32

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: rs9981861; hg19: chr21-41415044;