Genetic Variant NM_001389.5:c.5388A>T (chr21-40042669-T-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001389.5(DSCAM):c.5388A>T(p.Arg1796Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 1,214,538 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R1796R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000026 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DSCAM
NM_001389.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.122

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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=-0.122 with no splicing effect.

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.5388A>T	p.Arg1796Arg	synonymous	Exon 32 of 33	NP_001380.2
DSCAM	NM_001271534.3		c.5388A>T	p.Arg1796Arg	synonymous	Exon 32 of 33	NP_001258463.1
DSCAM	NR_073202.3		n.5694A>T		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.5388A>T	p.Arg1796Arg	synonymous	Exon 32 of 33	ENSP00000383303.1	O60469-1
DSCAM	ENST00000404019.2	TSL:1	c.4644A>T	p.Arg1548Arg	synonymous	Exon 28 of 29	ENSP00000385342.2	Q8WY19
DSCAM	ENST00000617870.4	TSL:5	c.4893A>T	p.Arg1631Arg	synonymous	Exon 29 of 30	ENSP00000478698.1	A0A087WUI7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

56266

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000263

AC:

AN:

1214538

Hom.:

Cov.:

AF XY:

0.0000392

AC XY:

AN XY:

586626

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000370

AC:

AN:

27014

American (AMR)

AF:

0.0000352

AC:

AN:

28392

Ashkenazi Jewish (ASJ)

AF:

0.0000484

AC:

AN:

20650

East Asian (EAS)

AF:

0.0000653

AC:

AN:

30634

South Asian (SAS)

AF:

0.000108

AC:

AN:

37018

European-Finnish (FIN)

AF:

0.0000252

AC:

AN:

39614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4846

European-Non Finnish (NFE)

AF:

0.0000205

AC:

AN:

977440

Other (OTH)

AF:

0.0000409

AC:

AN:

48930

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

56266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27480

African (AFR)

AF:

0.00

AC:

AN:

13314

American (AMR)

AF:

0.00

AC:

AN:

4700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1308

East Asian (EAS)

AF:

0.00

AC:

AN:

2440

South Asian (SAS)

AF:

0.00

AC:

AN:

2312

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

25600

Other (OTH)

AF:

0.00

AC:

AN:

652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.0

(source)

DANN

Benign

0.71

PhyloP100

-0.12

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