NM_001389.5:c.3019-7973A>T

Variant names:

• chr21-40152704-T-A
• rs11911749
• NM_001389.5:c.3019-7973A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B.

Score: -2 - Likely Benign

-2

PM2BP4_Strong

The NM_001389.5(DSCAM):​c.3019-7973A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 36)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.3019-7973A>T		intron_variant	Intron 16 of 32	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.3019-7973A>T		intron_variant	Intron 16 of 32		NP_001258463.1
DSCAM	NR_073202.3	n.3516-7973A>T		intron_variant	Intron 16 of 32
DSCAM	XM_017028281.2	c.2311-7973A>T		intron_variant	Intron 13 of 29		XP_016883770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.3019-7973A>T		intron_variant	Intron 16 of 32	1	NM_001389.5	ENSP00000383303.1
DSCAM	ENST00000404019.2	c.2275-7973A>T		intron_variant	Intron 12 of 28	1		ENSP00000385342.2
DSCAM	ENST00000617870.4	c.2524-7973A>T		intron_variant	Intron 13 of 29	5		ENSP00000478698.1

Frequencies

GnomAD3 genomes Cov.: 36

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

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.33
DANN	Benign	0.57
PhyloP100		-1.3

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: rs11911749; hg19: chr21-41524631;