chr4-1900811-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001042424.3(NSD2):c.157C>T(p.Leu53Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 32)
Consequence
NSD2
NM_001042424.3 missense
NM_001042424.3 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 3.26
Genes affected
NSD2 (HGNC:12766): (nuclear receptor binding SET domain protein 2) This gene encodes a protein that contains four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain, and a PHD-type zinc finger. It is expressed ubiquitously in early development. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene maps to the 165 kb WHS critical region and has also been involved in the chromosomal translocation t(4;14)(p16.3;q32.3) in multiple myelomas. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. Some transcript variants are nonsense-mediated mRNA (NMD) decay candidates, hence not represented as reference sequences. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25555342).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
32
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 | Aug 20, 2024 | The c.157C>T (p.L53F) alteration is located in exon 4 (coding exon 1) of the WHSC1 gene. This alteration results from a C to T substitution at nucleotide position 157, causing the leucine (L) at amino acid position 53 to be replaced by a phenylalanine (F). 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
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;T;.;T;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;.;D;D;.;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;L;.;L;L;L;L;L;.;L;L
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D
Sift4G
Benign
T;D;D;T;T;D;T;D;D;D;D
Polyphen
D;D;.;D;D;D;D;D;.;D;D
Vest4
MutPred
Gain of glycosylation at S56 (P = 0.0376);Gain of glycosylation at S56 (P = 0.0376);Gain of glycosylation at S56 (P = 0.0376);Gain of glycosylation at S56 (P = 0.0376);Gain of glycosylation at S56 (P = 0.0376);Gain of glycosylation at S56 (P = 0.0376);Gain of glycosylation at S56 (P = 0.0376);Gain of glycosylation at S56 (P = 0.0376);Gain of glycosylation at S56 (P = 0.0376);Gain of glycosylation at S56 (P = 0.0376);Gain of glycosylation at S56 (P = 0.0376);
MVP
MPC
0.93
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.