NM_001389.5:c.2182+749A>C

Variant names:

• chr21-40295306-T-G
• rs9977943
• NM_001389.5:c.2182+749A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001389.5(DSCAM):​c.2182+749A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,080 control chromosomes in the GnomAD database, including 7,232 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 0.30 (7232 hom., cov: 32)
• Consequence: DSCAM NM_001389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 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.2182+749A>C		intron	N/A	NP_001380.2
	DSCAM	NM_001271534.3		c.2182+749A>C		intron	N/A	NP_001258463.1
	DSCAM	NR_073202.3		n.2679+749A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.2182+749A>C		intron	N/A	ENSP00000383303.1
	DSCAM	ENST00000404019.2	TSL:1	c.1438+749A>C		intron	N/A	ENSP00000385342.2
	DSCAM	ENST00000617870.4	TSL:5	c.1687+749A>C		intron	N/A	ENSP00000478698.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45944 AN: 151962 Hom.: 7221 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.302 AC: 45997 AN: 152080 Hom.: 7232 Cov.: 32 AF XY: 0.306 AC XY: 22734 AN XY: 74338

African (AFR) AF: 0.241 AC: 10014 AN: 41502

American (AMR) AF: 0.304 AC: 4651 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1011 AN: 3468

East Asian (EAS) AF: 0.194 AC: 1000 AN: 5166

South Asian (SAS) AF: 0.389 AC: 1874 AN: 4822

European-Finnish (FIN) AF: 0.352 AC: 3714 AN: 10548

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22723 AN: 67974

Other (OTH) AF: 0.293 AC: 618 AN: 2112

Alfa AF: 0.326 Hom.: 13674

Bravo AF: 0.294

Asia WGS AF: 0.242 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.8
DANN	Benign	0.76
PhyloP100		-1.5
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: rs9977943; hg19: chr21-41667233;