Genetic Variant FRG2B:p.His11Tyr (chr10-133626712-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001080998.2(FRG2B):c.31C>T(p.His11Tyr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H11Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

FRG2B
NM_001080998.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.842

Publications

9 publications found

Variant links:

Genes affected

FRG2B (HGNC:33518): (FSHD region gene 2 family member B) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FRG2B links:

ENSG00000288107 (HGNC:):

ENSG00000288107 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.002344668).

BP6

Variant 10-133626712-G-A is Benign according to our data. Variant chr10-133626712-G-A is described in ClinVar as Benign. ClinVar VariationId is 402881.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRG2B	NM_001080998.2 link	c.31C>T	p.His11Tyr	missense_variant	Exon 1 of 4	ENST00000425520.2	NP_001074467.1	Q96QU4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FRG2B	ENST00000425520.2 link	c.31C>T	p.His11Tyr	missense_variant	Exon 1 of 4	1	NM_001080998.2	ENSP00000401310.1	Q96QU4
FRG2B	ENST00000443774.5 link	c.31C>T	p.His11Tyr	missense_variant	Exon 1 of 4	1		ENSP00000408343.1	A0A0A0MSZ2
ENSG00000288107	ENST00000655152.1 link	n.446-821G>A		intron_variant	Intron 1 of 1
ENSG00000288107	ENST00000669404.1 link	n.303-821G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.358

AC:

71497

AN:

199604

AF XY:

0.367

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.379

Gnomad EAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.455

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.319

Hom.:

ExAC

AF:

0.491

AC:

59617

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.8

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.081

.;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.53

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.97

.;L

PhyloP100

0.84

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.046

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.20

.;B

Vest4

0.27

MPC

1.7

ClinPred

0.019

GERP RS

0.11

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.18

gMVP

0.015

Mutation Taster

=99/1

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over