21-40011216-C-A

Variant summary

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

The NM_001389.5(DSCAM):c.*1818G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,066 control chromosomes in the GnomAD database, including 3,058 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 0.17 (3057 hom., cov: 32)
  • Exomes 𝑓: 0.20 (1 hom.)
• Consequence: DSCAM NM_001389.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSCAM	NM_001389.5	c.*1818G>T		3_prime_UTR_variant	33/33	ENST00000400454.6
DSCAM	NM_001271534.3	c.*1818G>T		3_prime_UTR_variant	33/33
DSCAM	NR_073202.3	n.8163G>T		non_coding_transcript_exon_variant	33/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSCAM	ENST00000400454.6	c.*1818G>T		3_prime_UTR_variant	33/33	1	NM_001389.5	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25824 AN: 151938 Hom.: 3041 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.170 AC: 25853 AN: 152056 Hom.: 3057 Cov.: 32 AF XY: 0.179 AC XY: 13335 AN XY: 74332

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.165

Alfa AF: 0.145 Hom.: 1203

Bravo AF: 0.186

Asia WGS AF: 0.302 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.3
Dann	Benign	0.73

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: rs2837371; hg19: chr21-41383143;