21-40042669-TCG-CCT

Variant names:

• chr21-40042669-TCG-CCT
• NM_001389.5:c.5386_5388delCGAinsAGG
• DSCAM p.1797

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001389.5(DSCAM):​c.5386_5388delCGAinsAGG​(p.1797) variant causes a splice region, synonymous change. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R1796R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 0)
• Consequence: DSCAM NM_001389.5 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07
• Publications: 0 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 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	NM_001389.5	MANE Select	c.5386_5388delCGAinsAGG	p.1797	splice_region synonymous	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.5386_5388delCGAinsAGG	p.1797	splice_region synonymous	N/A	NP_001258463.1
	DSCAM	NR_073202.3		n.5692_5694delCGAinsAGG		splice_region non_coding_transcript_exon	Exon 32 of 33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.5386_5388delCGAinsAGG	p.1797	splice_region synonymous	N/A	ENSP00000383303.1	O60469-1
	DSCAM	ENST00000404019.2	TSL:1	c.4642_4644delCGAinsAGG	p.1549	splice_region synonymous	N/A	ENSP00000385342.2	Q8WY19
	DSCAM	ENST00000617870.4	TSL:5	c.4891_4893delCGAinsAGG	p.1632	splice_region synonymous	N/A	ENSP00000478698.1	A0A087WUI7

Frequencies

GnomAD3 genomes Cov.: 0

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

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-41414596;