chr21-40044167-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001389.5(DSCAM):c.5294C>A(p.Thr1765Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
DSCAM
NM_001389.5 missense
NM_001389.5 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 4.70
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, DSCAM
BP4
?
Computational evidence support a benign effect (MetaRNN=0.26973218).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSCAM | NM_001389.5 | c.5294C>A | p.Thr1765Asn | missense_variant | 31/33 | ENST00000400454.6 | |
DSCAM | NM_001271534.3 | c.5294C>A | p.Thr1765Asn | missense_variant | 31/33 | ||
DSCAM | XM_017028281.2 | c.4586C>A | p.Thr1529Asn | missense_variant | 28/30 | ||
DSCAM | NR_073202.3 | n.5600C>A | non_coding_transcript_exon_variant | 31/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSCAM | ENST00000400454.6 | c.5294C>A | p.Thr1765Asn | missense_variant | 31/33 | 1 | NM_001389.5 | P1 | |
DSCAM | ENST00000404019.2 | c.4550C>A | p.Thr1517Asn | missense_variant | 27/29 | 1 | |||
DSCAM | ENST00000617870.4 | c.4799C>A | p.Thr1600Asn | missense_variant | 28/30 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.5294C>A (p.T1765N) alteration is located in exon 31 (coding exon 31) of the DSCAM gene. This alteration results from a C to A substitution at nucleotide position 5294, causing the threonine (T) at amino acid position 1765 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;D;D
Polyphen
P;.;.
Vest4
MutPred
Loss of glycosylation at T1765 (P = 0.0289);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.