11-117428428-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_020693.4(DSCAML1):c.6062G>A(p.Gly2021Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000277 in 1,550,756 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G2021G) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
DSCAML1
NM_020693.4 missense
NM_020693.4 missense
Scores
3
3
11
Clinical Significance
Conservation
PhyloP100: 5.63
Genes affected
DSCAML1 (HGNC:14656): (DS cell adhesion molecule like 1) The protein encoded by this gene is a member of the Ig superfamily of cell adhesion molecules and is involved in neuronal differentiation. The encoded membrane-bound protein localizes to the cell surface, where it forms aggregates that repel neuronal processes of the same cell type. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
Missense variant where missense usually causes diseases, DSCAML1
BS2
High AC in GnomAdExome4 at 41 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSCAML1 | NM_020693.4 | c.6062G>A | p.Gly2021Glu | missense_variant | 33/33 | ENST00000651296.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSCAML1 | ENST00000651296.2 | c.6062G>A | p.Gly2021Glu | missense_variant | 33/33 | NM_020693.4 | |||
DSCAML1 | ENST00000321322.6 | c.6242G>A | p.Gly2081Glu | missense_variant | 33/33 | 1 | P1 | ||
DSCAML1 | ENST00000651172.1 | c.6242G>A | p.Gly2081Glu | missense_variant | 33/33 | P1 | |||
DSCAML1 | ENST00000527706.5 | c.5432G>A | p.Gly1811Glu | missense_variant | 31/31 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152074Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000102 AC: 2AN: 196598Hom.: 0 AF XY: 0.00000929 AC XY: 1AN XY: 107646
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GnomAD4 exome AF: 0.0000293 AC: 41AN: 1398682Hom.: 0 Cov.: 33 AF XY: 0.0000362 AC XY: 25AN XY: 691200
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152074Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74290
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 08, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2081 of the DSCAML1 protein (p.Gly2081Glu). This variant is present in population databases (no rsID available, gnomAD 0.01%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1923822). This variant has not been reported in the literature in individuals affected with DSCAML1-related conditions. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Vest4
MVP
MPC
0.0091
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at