Genetic Variant EXTL2:p.Ser278Arg (chr1-100874101-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001033025.3(EXTL2):c.834T>A(p.Ser278Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,612,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

EXTL2
NM_001033025.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.216

Publications

1 publications found

Variant links:

Genes affected

EXTL2 (HGNC:3516): (exostosin like glycosyltransferase 2) Enables alpha-1,4-N-acetylgalactosaminyltransferase activity and glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity. Involved in N-acetylglucosamine metabolic process and UDP-N-acetylgalactosamine metabolic process. Located in cytosol; endoplasmic reticulum; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

EXTL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23856714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033025.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXTL2	NM_001033025.3	MANE Select	c.834T>A	p.Ser278Arg	missense	Exon 5 of 5	NP_001028197.1	Q9UBQ6
EXTL2	NM_001261441.2		c.858T>A	p.Ser286Arg	missense	Exon 6 of 6	NP_001248370.1
EXTL2	NM_001439.4		c.834T>A	p.Ser278Arg	missense	Exon 5 of 5	NP_001430.1	Q9UBQ6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXTL2	ENST00000370114.8	TSL:1 MANE Select	c.834T>A	p.Ser278Arg	missense	Exon 5 of 5	ENSP00000359132.3	Q9UBQ6
EXTL2	ENST00000370113.7	TSL:1	c.834T>A	p.Ser278Arg	missense	Exon 5 of 5	ENSP00000359131.3	Q9UBQ6
EXTL2	ENST00000886545.1		c.858T>A	p.Ser286Arg	missense	Exon 6 of 6	ENSP00000556603.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000399

AC:

AN:

250896

AF XY:

0.0000516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000418

AC:

AN:

1460930

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

726766

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.0000540

AC:

AN:

1111566

Other (OTH)

AF:

0.0000166

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67962

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.045

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.32

MutationAssessor

Pathogenic

3.0

PhyloP100

0.22

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.46

Sift

Benign

0.071

Sift4G

Uncertain

0.0060

Polyphen

0.78

Vest4

0.14

MutPred

0.60

Gain of MoRF binding (P = 0.043)

MVP

0.84

MPC

0.48

ClinPred

0.67

GERP RS

-0.038

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.58

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over