chr21-40042663-T-C

Position:

• chr21-40042663-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001389.5(DSCAM):​c.5394A>G​(p.Arg1798=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,289,608 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0036 (5 hom.)
• Consequence: DSCAM NM_001389.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.320

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 21-40042663-T-C is Benign according to our data. Variant chr21-40042663-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 778180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.32 with no splicing effect.
• BS2: High AC in GnomAd4 at 307 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCAM	NM_001389.5	c.5394A>G	p.Arg1798=	synonymous_variant	32/33	ENST00000400454.6	NP_001380.2
DSCAM	NM_001271534.3	c.5394A>G	p.Arg1798=	synonymous_variant	32/33		NP_001258463.1
DSCAM	XM_017028281.2	c.4686A>G	p.Arg1562=	synonymous_variant	29/30		XP_016883770.1
DSCAM	NR_073202.3	n.5700A>G		non_coding_transcript_exon_variant	32/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6	c.5394A>G	p.Arg1798=	synonymous_variant	32/33	1	NM_001389.5	ENSP00000383303	P1
DSCAM	ENST00000404019.2	c.4650A>G	p.Arg1550=	synonymous_variant	28/29	1		ENSP00000385342
DSCAM	ENST00000617870.4	c.4899A>G	p.Arg1633=	synonymous_variant	29/30	5		ENSP00000478698

Frequencies

GnomAD3 genomes AF: 0.00481 AC: 307 AN: 63762 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00436

Gnomad ASJ AF: 0.00765

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00720

Gnomad OTH AF: 0.00390

GnomAD3 exomes AF: 0.00293 AC: 595 AN: 202904 Hom.: 0 AF XY: 0.00280 AC XY: 310 AN XY: 110808

Gnomad AFR exome AF: 0.000327

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00364

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00437

Gnomad NFE exome AF: 0.00422

Gnomad OTH exome AF: 0.00257

GnomAD4 exome AF: 0.00356 AC: 4367 AN: 1225726 Hom.: 5 Cov.: 31 AF XY: 0.00358 AC XY: 2126 AN XY: 593624

Gnomad4 AFR exome AF: 0.000618

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.00467

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00439

Gnomad4 NFE exome AF: 0.00391

Gnomad4 OTH exome AF: 0.00337

GnomAD4 genome AF: 0.00481 AC: 307 AN: 63882 Hom.: 0 Cov.: 0 AF XY: 0.00446 AC XY: 142 AN XY: 31860

Gnomad4 AFR AF: 0.00172

Gnomad4 AMR AF: 0.00435

Gnomad4 ASJ AF: 0.00765

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00565

Gnomad4 NFE AF: 0.00720

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.00208 Hom.: 0

Bravo AF: 0.00192

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 31, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	DSCAM: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.6
DANN	Benign	0.62

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: rs200764944; hg19: chr21-41414590;