11-44107944-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207122.2(EXT2):​c.232C>T​(p.Pro78Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P78A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EXT2
NM_207122.2 missense

Scores

2
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.74
Variant links:
Genes affected
EXT2 (HGNC:3513): (exostosin glycosyltransferase 2) This gene encodes one of two glycosyltransferases involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type II form of multiple exostoses. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [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=0.25854048).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EXT2NM_207122.2 linkc.232C>T p.Pro78Ser missense_variant Exon 2 of 14 ENST00000533608.7 NP_997005.1 Q93063-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EXT2ENST00000533608.7 linkc.232C>T p.Pro78Ser missense_variant Exon 2 of 14 1 NM_207122.2 ENSP00000431173.2 Q93063-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461886
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Benign
-0.075
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T;.;.;.;T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.069
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
.;D;D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.26
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.97
L;.;L;.;L
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.080
N;D;N;N;N
REVEL
Benign
0.038
Sift
Benign
0.23
T;D;T;T;T
Sift4G
Benign
0.85
T;D;T;T;T
Polyphen
0.041
B;.;B;.;B
Vest4
0.35
MutPred
0.28
Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);.;Gain of loop (P = 0.0502);
MVP
0.73
MPC
0.23
ClinPred
0.89
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.099
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-44129494; API