rs587778299

chr11-44107944-C-Achr11-44107944-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_207122.2(EXT2):c.232C>A(p.Pro78Thr) 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. 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)
• Consequence: EXT2 NM_207122.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29994678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT2	NM_207122.2	c.232C>A	p.Pro78Thr	missense_variant	2/14	ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.232C>A	p.Pro78Thr	missense_variant	2/14	1	NM_207122.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.;.;.;T
Eigen	Benign	-0.022
Eigen_PC	Benign	0.092
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.30	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;.;L;.;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.76	N;D;N;N;N
REVEL	Benign	0.098
Sift	Benign	0.066	T;D;D;D;T
Sift4G	Benign	0.21	T;D;T;T;T
Polyphen		0.23	B;.;B;.;B
Vest4		0.69
MutPred		0.30		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		0.76
MPC		0.26
ClinPred		0.84	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.78

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;