dbSNP rs2837371: DSCAM:c.*1818G>T (chr21-40011216-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001389.5(DSCAM):c.*1818G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,066 control chromosomes in the GnomAD database, including 3,058 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 0.17 ( 3057 hom., cov: 32)

Exomes 𝑓: 0.20 ( 1 hom. )

Consequence

DSCAM
NM_001389.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.131

Publications

2 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DSCAM	NM_001389.5 link	c.*1818G>T	3_prime_UTR_variant	Exon 33 of 33	ENST00000400454.6	NP_001380.2	O60469-1
DSCAM	NR_073202.3 link	n.8163G>T	non_coding_transcript_exon_variant	Exon 33 of 33
DSCAM	NM_001271534.3 link	c.*1818G>T	3_prime_UTR_variant	Exon 33 of 33		NP_001258463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSCAM	ENST00000400454.6 link	c.*1818G>T		3_prime_UTR_variant	Exon 33 of 33	1	NM_001389.5	ENSP00000383303.1		O60469-1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25824

AN:

151938

Hom.:

3041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.164

GnomAD4 exome

AF:

0.200

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.170

AC:

25853

AN:

152056

Hom.:

3057

Cov.:

AF XY:

0.179

AC XY:

13335

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.121

AC:

5007

AN:

41478

American (AMR)

AF:

0.371

AC:

5662

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

493

AN:

3472

East Asian (EAS)

AF:

0.390

AC:

2011

AN:

5152

South Asian (SAS)

AF:

0.292

AC:

1405

AN:

4808

European-Finnish (FIN)

AF:

0.183

AC:

1929

AN:

10552

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.129

AC:

8744

AN:

67998

Other (OTH)

AF:

0.165

AC:

348

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1001

2003

3004

4006

5007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.142

Hom.:

1620

Bravo

AF:

0.186

Asia WGS

AF:

0.302

AC:

1045

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.3

(source)

DANN

Benign

0.73

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over