Genetic Variant DSCAM:p.Asp1994Tyr (chr21-40013093-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001389.5(DSCAM):c.5980G>T(p.Asp1994Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1994N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DSCAM
NM_001389.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.34

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.5980G>T	p.Asp1994Tyr	missense	Exon 33 of 33	NP_001380.2
DSCAM	NM_001271534.3		c.5926G>T	p.Asp1976Tyr	missense	Exon 33 of 33	NP_001258463.1
DSCAM	NR_073202.3		n.6286G>T		non_coding_transcript_exon	Exon 33 of 33

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.5980G>T	p.Asp1994Tyr	missense	Exon 33 of 33	ENSP00000383303.1	O60469-1
DSCAM	ENST00000404019.2	TSL:1	c.5182G>T	p.Asp1728Tyr	missense	Exon 29 of 29	ENSP00000385342.2	Q8WY19
DSCAM	ENST00000617870.4	TSL:5	c.5485G>T	p.Asp1829Tyr	missense	Exon 30 of 30	ENSP00000478698.1	A0A087WUI7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1439076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712668

African (AFR)

AF:

0.00

AC:

AN:

32984

American (AMR)

AF:

0.00

AC:

AN:

42546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25148

East Asian (EAS)

AF:

0.00

AC:

AN:

39206

South Asian (SAS)

AF:

0.00

AC:

AN:

82502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098470

Other (OTH)

AF:

0.00

AC:

AN:

59450

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

-0.0071

MutationAssessor

Benign

1.9

PhyloP100

7.3

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.76

MutPred

0.20

Gain of phosphorylation at D1994 (P = 0.0271)

MVP

0.87

MPC

0.66

ClinPred

0.96

GERP RS

5.4

Varity_R

0.51

gMVP

0.44

Mutation Taster

=16/84

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