21-40042427-T-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The ENST00000400454.6(DSCAM):c.5630A>T(p.Lys1877Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
DSCAM
ENST00000400454.6 missense
ENST00000400454.6 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 7.92
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 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DSCAM. . Gene score misZ 3.2228 (greater than the threshold 3.09). Trascript score misZ 4.4297 (greater than threshold 3.09). GenCC has associacion of gene with autism spectrum disorder.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSCAM | NM_001389.5 | c.5630A>T | p.Lys1877Ile | missense_variant | 32/33 | ENST00000400454.6 | NP_001380.2 | |
DSCAM | NM_001271534.3 | c.5630A>T | p.Lys1877Ile | missense_variant | 32/33 | NP_001258463.1 | ||
DSCAM | XM_017028281.2 | c.4922A>T | p.Lys1641Ile | missense_variant | 29/30 | XP_016883770.1 | ||
DSCAM | NR_073202.3 | n.5936A>T | non_coding_transcript_exon_variant | 32/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DSCAM | ENST00000400454.6 | c.5630A>T | p.Lys1877Ile | missense_variant | 32/33 | 1 | NM_001389.5 | ENSP00000383303 | P1 | |
DSCAM | ENST00000404019.2 | c.4886A>T | p.Lys1629Ile | missense_variant | 28/29 | 1 | ENSP00000385342 | |||
DSCAM | ENST00000617870.4 | c.5135A>T | p.Lys1712Ile | missense_variant | 29/30 | 5 | ENSP00000478698 |
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 | Jan 04, 2024 | The c.5630A>T (p.K1877I) alteration is located in exon 32 (coding exon 32) of the DSCAM gene. This alteration results from a A to T substitution at nucleotide position 5630, causing the lysine (K) at amino acid position 1877 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D
REVEL
Uncertain
Sift
Uncertain
D;.;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of catalytic residue at K1877 (P = 9e-04);.;.;
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.