Variant 11-44095958-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_207122.2(EXT2):c.-31+106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 427,184 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0099 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 15 hom. )

Consequence

EXT2
NM_207122.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.299

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]

EXT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-44095958-C-T is Benign according to our data. Variant chr11-44095958-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1321817.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00988 (1504/152200) while in subpopulation AFR AF= 0.0332 (1379/41554). AF 95% confidence interval is 0.0317. There are 28 homozygotes in gnomad4. There are 751 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1504 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
EXT2	NM_207122.2 linkuse as main transcript	c.-31+106C>T	intron_variant	ENST00000533608.7	NP_997005.1
EXT2	NM_001178083.3 linkuse as main transcript	c.-31+106C>T	intron_variant		NP_001171554.1
EXT2	NM_001389630.1 linkuse as main transcript	c.-70+106C>T	intron_variant		NP_001376559.1
EXT2	XM_047426529.1 linkuse as main transcript	c.-183+106C>T	intron_variant		XP_047282485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXT2	ENST00000533608.7 linkuse as main transcript	c.-31+106C>T		intron_variant		1	NM_207122.2	ENSP00000431173	P1	Q93063-1

Frequencies

GnomAD3 genomes

AF:

0.00984

AC:

1497

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00717

GnomAD4 exome

AF:

0.00320

AC:

880

AN:

274984

Hom.:

AF XY:

0.00382

AC XY:

566

AN XY:

148056

show subpopulations

Gnomad4 AFR exome

AF:

0.0339

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00523

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.0000683

Gnomad4 NFE exome

AF:

0.000205

Gnomad4 OTH exome

AF:

0.00421

GnomAD4 genome

AF:

0.00988

AC:

1504

AN:

152200

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

751

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0332

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00233

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00707

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00722

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.9

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over