rs199916419

Positions:

• chr11-44108135-C-G
• chr11-44108135-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_207122.2(EXT2):​c.423C>G​(p.Asp141Glu) 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. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EXT2 NM_207122.2 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.961

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXT2	NM_207122.2	c.423C>G	p.Asp141Glu	missense_variant	2/14	ENST00000533608.7	NP_997005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXT2	ENST00000533608.7	c.423C>G	p.Asp141Glu	missense_variant	2/14	1	NM_207122.2	ENSP00000431173	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Uncertain	0.54	D;.;.;D
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	.;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	-0.27	N;N;.;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.65	N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.92	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.079
MutPred		0.57		Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);.;Gain of sheet (P = 0.1945);
MVP		1.0
MPC		0.20
ClinPred		0.35	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.076
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.75		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.75		Position offset: -5

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

Publications

LitVar

Other links and lift over

dbSNP: rs199916419; hg19: chr11-44129685;