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GeneBe

21-40042603-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001389.5(DSCAM):c.5454C>T(p.Tyr1818=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

DSCAM
NM_001389.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.107
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 21-40042603-G-A is Benign according to our data. Variant chr21-40042603-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652669.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.107 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DSCAMNM_001389.5 linkuse as main transcriptc.5454C>T p.Tyr1818= synonymous_variant 32/33 ENST00000400454.6
DSCAMNM_001271534.3 linkuse as main transcriptc.5454C>T p.Tyr1818= synonymous_variant 32/33
DSCAMXM_017028281.2 linkuse as main transcriptc.4746C>T p.Tyr1582= synonymous_variant 29/30
DSCAMNR_073202.3 linkuse as main transcriptn.5760C>T non_coding_transcript_exon_variant 32/33

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DSCAMENST00000400454.6 linkuse as main transcriptc.5454C>T p.Tyr1818= synonymous_variant 32/331 NM_001389.5 P1O60469-1
DSCAMENST00000404019.2 linkuse as main transcriptc.4710C>T p.Tyr1570= synonymous_variant 28/291
DSCAMENST00000617870.4 linkuse as main transcriptc.4959C>T p.Tyr1653= synonymous_variant 29/305

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000210
AC:
32
AN:
152116
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000256
AC:
64
AN:
249538
Hom.:
0
AF XY:
0.000303
AC XY:
41
AN XY:
135384
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.000458
Gnomad FIN exome
AF:
0.000372
Gnomad NFE exome
AF:
0.000256
Gnomad OTH exome
AF:
0.000330
GnomAD4 exome
AF:
0.000244
AC:
357
AN:
1461850
Hom.:
0
Cov.:
31
AF XY:
0.000242
AC XY:
176
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000246
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.000417
Gnomad4 FIN exome
AF:
0.000337
Gnomad4 NFE exome
AF:
0.000249
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000210
AC:
32
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.000215
AC XY:
16
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000249
Hom.:
0
Bravo
AF:
0.000189
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2023DSCAM: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
4.2
Dann
Benign
0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199512904; hg19: chr21-41414530; COSMIC: COSV68027234; API