rs2837754

chr21-40619133-G-A

Variant summary

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

The NM_001389.5(DSCAM):c.508+73677C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,142 control chromosomes in the GnomAD database, including 1,368 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 0.12 (1368 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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-IT1 (HGNC:41327): (DSCAM intronic transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSCAM	NM_001389.5	c.508+73677C>T		intron_variant		ENST00000400454.6
DSCAM-IT1	NR_046774.2	n.359-265C>T		intron_variant, non_coding_transcript_variant
DSCAM	NM_001271534.3	c.508+73677C>T		intron_variant
DSCAM	NR_073202.3	n.1005+73677C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSCAM	ENST00000400454.6	c.508+73677C>T		intron_variant		1	NM_001389.5	P1
DSCAM-IT1	ENST00000441910.5	n.358+2122C>T		intron_variant, non_coding_transcript_variant		5
DSCAM-IT1	ENST00000440363.1	n.359-265C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17550 AN: 152024 Hom.: 1367 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0790

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.115 AC: 17546 AN: 152142 Hom.: 1368 Cov.: 32 AF XY: 0.112 AC XY: 8321 AN XY: 74396

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0522

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0383

Gnomad4 NFE AF: 0.0790

Gnomad4 OTH AF: 0.0867

Alfa AF: 0.0877 Hom.: 360

Bravo AF: 0.118

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.7
Dann	Benign	0.41

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: rs2837754; hg19: chr21-41991059;