Variant 21-40083927-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
DSCAM	NM_001389.5 linkuse as main transcript	c.4212C>T	p.Asn1404=	synonymous_variant	24/33	ENST00000400454.6
DSCAM	NM_001271534.3 linkuse as main transcript	c.4212C>T	p.Asn1404=	synonymous_variant	24/33
DSCAM	XM_017028281.2 linkuse as main transcript	c.3504C>T	p.Asn1168=	synonymous_variant	21/30
DSCAM	NR_073202.3 linkuse as main transcript	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 linkuse as main transcript	c.4212C>T	p.Asn1404=	synonymous_variant	24/33	1	NM_001389.5	P1	O60469-1
DSCAM	ENST00000404019.2 linkuse as main transcript	c.3468C>T	p.Asn1156=	synonymous_variant	20/29	1
DSCAM	ENST00000617870.4 linkuse as main transcript	c.3717C>T	p.Asn1239=	synonymous_variant	21/30	5

Frequencies

GnomAD3 genomes

AF:

0.0627

AC:

9532

AN:

152106

Hom.:

412

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0493

AC XY:

35796

AN XY:

726550

show subpopulations

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.:

AF XY:

0.0609

AC XY:

4533

AN XY:

74418

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over