21-40619133-G-A

Variant names:

• chr21-40619133-G-A
• rs2837754
• NM_001389.5:c.508+73677C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	NM_001389.5	MANE Select	c.508+73677C>T		intron	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.508+73677C>T		intron	N/A	NP_001258463.1
	DSCAM-IT1	NR_046774.2		n.359-265C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.508+73677C>T		intron	N/A	ENSP00000383303.1
	DSCAM-IT1	ENST00000440363.1	TSL:3	n.359-265C>T		intron	N/A
	DSCAM-IT1	ENST00000441910.5	TSL:5	n.358+2122C>T		intron	N/A

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

African (AFR) AF: 0.220 AC: 9122 AN: 41464

American (AMR) AF: 0.0522 AC: 798 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3470

East Asian (EAS) AF: 0.140 AC: 723 AN: 5178

South Asian (SAS) AF: 0.154 AC: 742 AN: 4812

European-Finnish (FIN) AF: 0.0383 AC: 406 AN: 10608

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0790 AC: 5374 AN: 68004

Other (OTH) AF: 0.0867 AC: 183 AN: 2110

Alfa AF: 0.0881 Hom.: 397

Bravo AF: 0.118

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.7
DANN	Benign	0.41
PhyloP100		0.070
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2837754; hg19: chr21-41991059;