chr21-40083927-G-A

Position:

• chr21-40083927-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001389.5(DSCAM):​c.4212C>T​(p.Asn1404=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 1,612,644 control chromosomes in the GnomAD database, including 2,564 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 0.063 (413 hom., cov: 33)
  • Exomes 𝑓: 0.051 (2151 hom.)
• Consequence: DSCAM NM_001389.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSCAM	NM_001389.5	c.4212C>T	p.Asn1404=	synonymous_variant	24/33	ENST00000400454.6
DSCAM	NM_001271534.3	c.4212C>T	p.Asn1404=	synonymous_variant	24/33
DSCAM	XM_017028281.2	c.3504C>T	p.Asn1168=	synonymous_variant	21/30
DSCAM	NR_073202.3	n.4709C>T		non_coding_transcript_exon_variant	24/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSCAM	ENST00000400454.6	c.4212C>T	p.Asn1404=	synonymous_variant	24/33	1	NM_001389.5	P1
DSCAM	ENST00000404019.2	c.3468C>T	p.Asn1156=	synonymous_variant	20/29	1
DSCAM	ENST00000617870.4	c.3717C>T	p.Asn1239=	synonymous_variant	21/30	5

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9532 AN: 152106 Hom.: 412 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0506

Gnomad OTH AF: 0.0473

GnomAD3 exomes AF: 0.0452 AC: 11228 AN: 248396 Hom.: 427 AF XY: 0.0437 AC XY: 5894 AN XY: 134794

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.0252

Gnomad ASJ exome AF: 0.0205

Gnomad EAS exome AF: 0.120

Gnomad SAS exome AF: 0.0149

Gnomad FIN exome AF: 0.0196

Gnomad NFE exome AF: 0.0473

Gnomad OTH exome AF: 0.0408

GnomAD4 exome AF: 0.0506 AC: 73827 AN: 1460420 Hom.: 2151 Cov.: 30 AF XY: 0.0493 AC XY: 35796 AN XY: 726550

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0265

Gnomad4 ASJ exome AF: 0.0199

Gnomad4 EAS exome AF: 0.0920

Gnomad4 SAS exome AF: 0.0146

Gnomad4 FIN exome AF: 0.0206

Gnomad4 NFE exome AF: 0.0535

Gnomad4 OTH exome AF: 0.0539

GnomAD4 genome AF: 0.0627 AC: 9545 AN: 152224 Hom.: 413 Cov.: 33 AF XY: 0.0609 AC XY: 4533 AN XY: 74418

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0422

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.0196

Gnomad4 NFE AF: 0.0506

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0513 Hom.: 331

Bravo AF: 0.0663

Asia WGS AF: 0.0900 AC: 314 AN: 3478

EpiCase AF: 0.0431

EpiControl AF: 0.0455

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.11
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2297263; hg19: chr21-41455854; COSMIC: COSV68021707;