rs2222973

chr21-40461957-T-Cchr21-40461957-T-A

Variant summary

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

The NM_001389.5(DSCAM):c.509-92712A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,082 control chromosomes in the GnomAD database, including 10,878 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 0.36 (10878 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSCAM	NM_001389.5	c.509-92712A>G		intron_variant		ENST00000400454.6
DSCAM	NM_001271534.3	c.509-92712A>G		intron_variant
DSCAM	NR_073202.3	n.1006-92712A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSCAM	ENST00000400454.6	c.509-92712A>G		intron_variant		1	NM_001389.5	P1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54114 AN: 151964 Hom.: 10841 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.356 AC: 54195 AN: 152082 Hom.: 10878 Cov.: 32 AF XY: 0.358 AC XY: 26576 AN XY: 74318

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.332

Alfa AF: 0.287 Hom.: 11094

Bravo AF: 0.372

Asia WGS AF: 0.384 AC: 1335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.031
Dann	Benign	0.42

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: rs2222973; hg19: chr21-41833884;