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GeneBe

21-40042669-T-G

Variant summary

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

The NM_001389.5(DSCAM):c.5388A>C(p.Arg1796=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,271,104 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00075 ( 4 hom. )

Consequence

DSCAM
NM_001389.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.122
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=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 21-40042669-T-G is Benign according to our data. Variant chr21-40042669-T-G is described in ClinVar as [Benign]. Clinvar id is 742975.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=-0.122 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 78 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DSCAMNM_001389.5 linkuse as main transcriptc.5388A>C p.Arg1796= synonymous_variant 32/33 ENST00000400454.6
DSCAMNM_001271534.3 linkuse as main transcriptc.5388A>C p.Arg1796= synonymous_variant 32/33
DSCAMXM_017028281.2 linkuse as main transcriptc.4680A>C p.Arg1560= synonymous_variant 29/30
DSCAMNR_073202.3 linkuse as main transcriptn.5694A>C 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.5388A>C p.Arg1796= synonymous_variant 32/331 NM_001389.5 P1O60469-1
DSCAMENST00000404019.2 linkuse as main transcriptc.4644A>C p.Arg1548= synonymous_variant 28/291
DSCAMENST00000617870.4 linkuse as main transcriptc.4893A>C p.Arg1631= synonymous_variant 29/305

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00139
AC:
78
AN:
56274
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000451
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00447
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00605
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0294
Gnomad NFE
AF:
0.00129
Gnomad OTH
AF:
0.00153
GnomAD3 exomes
AF:
0.00107
AC:
205
AN:
191766
Hom.:
1
AF XY:
0.00134
AC XY:
141
AN XY:
105048
show subpopulations
Gnomad AFR exome
AF:
0.0000834
Gnomad AMR exome
AF:
0.000677
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00578
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000641
Gnomad OTH exome
AF:
0.00185
GnomAD4 exome
AF:
0.000752
AC:
913
AN:
1214706
Hom.:
4
Cov.:
31
AF XY:
0.000943
AC XY:
553
AN XY:
586716
show subpopulations
Gnomad4 AFR exome
AF:
0.000407
Gnomad4 AMR exome
AF:
0.000810
Gnomad4 ASJ exome
AF:
0.0000968
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00885
Gnomad4 FIN exome
AF:
0.0000505
Gnomad4 NFE exome
AF:
0.000470
Gnomad4 OTH exome
AF:
0.00125
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00137
AC:
77
AN:
56398
Hom.:
0
Cov.:
0
AF XY:
0.00145
AC XY:
40
AN XY:
27624
show subpopulations
Gnomad4 AFR
AF:
0.000446
Gnomad4 AMR
AF:
0.00446
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00563
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00129
Gnomad4 OTH
AF:
0.00149
Alfa
AF:
0.00145
Hom.:
0

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
5.2
Dann
Benign
0.69

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: rs181977833; hg19: chr21-41414596; API