Genetic Variant NM_001389.5:c.5260C>G (chr21-40044201-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001389.5(DSCAM):c.5260C>G(p.Arg1754Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DSCAM
NM_001389.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.29

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28657478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5 link	c.5260C>G	p.Arg1754Gly	missense_variant	Exon 31 of 33	ENST00000400454.6	NP_001380.2	O60469-1
DSCAM	NM_001271534.3 link	c.5260C>G	p.Arg1754Gly	missense_variant	Exon 31 of 33		NP_001258463.1
DSCAM	XM_017028281.2 link	c.4552C>G	p.Arg1518Gly	missense_variant	Exon 28 of 30		XP_016883770.1
DSCAM	NR_073202.3 link	n.5566C>G		non_coding_transcript_exon_variant	Exon 31 of 33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DSCAM	ENST00000400454.6 link	c.5260C>G	p.Arg1754Gly	missense_variant	Exon 31 of 33	1	NM_001389.5	ENSP00000383303.1	O60469-1
DSCAM	ENST00000404019.2 link	c.4516C>G	p.Arg1506Gly	missense_variant	Exon 27 of 29	1		ENSP00000385342.2	Q8WY19
DSCAM	ENST00000617870.4 link	c.4765C>G	p.Arg1589Gly	missense_variant	Exon 28 of 30	5		ENSP00000478698.1	A0A087WUI7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.078

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.9

L;.;.

PhyloP100

1.3

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.5

D;.;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.012

D;.;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.75

MutPred

0.27

Loss of sheet (P = 0.0228);.;.;

MVP

0.84

MPC

1.5

ClinPred

0.96

GERP RS

1.7

Varity_R

0.36

gMVP

0.70

Mutation Taster

=43/57

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over