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.

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	Effect	Exon Rank	Protein
DSCAM	NM_001389.5	MANE Select	c.*1818G>T	3_prime_UTR	Exon 33 of 33	NP_001380.2
DSCAM	NM_001271534.3		c.*1818G>T	3_prime_UTR	Exon 33 of 33	NP_001258463.1
DSCAM	NR_073202.3		n.8163G>T	non_coding_transcript_exon	Exon 33 of 33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAM	ENST00000400454.6	TSL:1 MANE Select	c.*1818G>T		3_prime_UTR	Exon 33 of 33	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over