chr21-40044143-G-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_001389.5(DSCAM):c.5318C>A(p.Pro1773His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,858 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
DSCAM
NM_001389.5 missense
NM_001389.5 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 7.84
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 Likely_benign. Variant got -4 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, DSCAM
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3978083).
BS2
?
High AC in GnomAdExome at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSCAM | NM_001389.5 | c.5318C>A | p.Pro1773His | missense_variant | 31/33 | ENST00000400454.6 | |
DSCAM | NM_001271534.3 | c.5318C>A | p.Pro1773His | missense_variant | 31/33 | ||
DSCAM | XM_017028281.2 | c.4610C>A | p.Pro1537His | missense_variant | 28/30 | ||
DSCAM | NR_073202.3 | n.5624C>A | non_coding_transcript_exon_variant | 31/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSCAM | ENST00000400454.6 | c.5318C>A | p.Pro1773His | missense_variant | 31/33 | 1 | NM_001389.5 | P1 | |
DSCAM | ENST00000404019.2 | c.4574C>A | p.Pro1525His | missense_variant | 27/29 | 1 | |||
DSCAM | ENST00000617870.4 | c.4823C>A | p.Pro1608His | missense_variant | 28/30 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249618Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135406
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727224
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
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3
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 | Jul 09, 2021 | The c.5318C>A (p.P1773H) 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 5318, causing the proline (P) at amino acid position 1773 to be replaced by a histidine (H). 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
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.;N
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0646);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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Score
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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