Genetic Variant DSCAM:p.Ser1799Asn (chr21-40042661-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001389.5(DSCAM):c.5396G>A(p.Ser1799Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000771 in 1,296,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

DSCAM
NM_001389.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

DSCAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19837171).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DSCAM	NM_001389.5	MANE Select	c.5396G>A	p.Ser1799Asn	missense	Exon 32 of 33	NP_001380.2
DSCAM	NM_001271534.3		c.5396G>A	p.Ser1799Asn	missense	Exon 32 of 33	NP_001258463.1
DSCAM	NR_073202.3		n.5702G>A		non_coding_transcript_exon	Exon 32 of 33

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.5396G>A	p.Ser1799Asn	missense	Exon 32 of 33	ENSP00000383303.1	O60469-1
DSCAM	ENST00000404019.2	TSL:1	c.4652G>A	p.Ser1551Asn	missense	Exon 28 of 29	ENSP00000385342.2	Q8WY19
DSCAM	ENST00000617870.4	TSL:5	c.4901G>A	p.Ser1634Asn	missense	Exon 29 of 30	ENSP00000478698.1	A0A087WUI7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.71e-7

AC:

AN:

1296242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

634744

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29168

American (AMR)

AF:

0.00

AC:

AN:

36336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22674

East Asian (EAS)

AF:

0.00

AC:

AN:

32988

South Asian (SAS)

AF:

0.00

AC:

AN:

52932

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5216

European-Non Finnish (NFE)

AF:

9.80e-7

AC:

AN:

1020302

Other (OTH)

AF:

0.00

AC:

AN:

52690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.044

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.80

M_CAP

Benign

0.010

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.90

PhyloP100

3.4

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

1.2

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

0.78

Polyphen

0.99

Vest4

0.33

MutPred

0.13

Loss of phosphorylation at S1799 (P = 0.0017)

MVP

0.65

MPC

0.50

ClinPred

0.76

GERP RS

5.3

Varity_R

0.15

gMVP

0.65

Mutation Taster

=47/53

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over