Variant 21-40044069-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001389.5(DSCAM):c.5383+9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,613,010 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 7 hom. )

Consequence

DSCAM
NM_001389.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.23

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 21-40044069-A-T is Benign according to our data. Variant chr21-40044069-A-T is described in ClinVar as [Benign]. Clinvar id is 787505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00103 (1504/1460684) while in subpopulation MID AF= 0.0222 (108/4866). AF 95% confidence interval is 0.0188. There are 7 homozygotes in gnomad4_exome. There are 744 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 332 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
DSCAM	NM_001389.5 linkuse as main transcript	c.5383+9T>A	intron_variant	ENST00000400454.6
DSCAM	NM_001271534.3 linkuse as main transcript	c.5383+9T>A	intron_variant
DSCAM	XM_017028281.2 linkuse as main transcript	c.4675+9T>A	intron_variant
DSCAM	NR_073202.3 linkuse as main transcript	n.5689+9T>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
DSCAM	ENST00000400454.6 linkuse as main transcript	c.5383+9T>A	intron_variant	1	NM_001389.5	P1	O60469-1
DSCAM	ENST00000404019.2 linkuse as main transcript	c.4639+9T>A	intron_variant	1
DSCAM	ENST00000617870.4 linkuse as main transcript	c.4888+9T>A	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

332

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00407

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00152

AC:

378

AN:

249234

Hom.:

AF XY:

0.00146

AC XY:

197

AN XY:

135162

show subpopulations

Gnomad AFR exome

AF:

0.00412

Gnomad AMR exome

AF:

0.00284

Gnomad ASJ exome

AF:

0.000895

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000883

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.00446

GnomAD4 exome

AF:

0.00103

AC:

1504

AN:

1460684

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

744

AN XY:

726638

show subpopulations

Gnomad4 AFR exome

AF:

0.00469

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000685

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000825

Gnomad4 OTH exome

AF:

0.00206

GnomAD4 genome

AF:

0.00218

AC:

332

AN:

152326

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00406

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.00247

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00213

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

DSCAM-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 21, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

DANN

Benign

0.47

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over