rs79777505

Positions:

• chr10-133626712-G-A
• chr10-133626712-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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. 12/20 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.842

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 402881.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRG2B	NM_001080998.2	c.31C>T	p.His11Tyr	missense_variant	1/4	ENST00000425520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRG2B	ENST00000425520.2	c.31C>T	p.His11Tyr	missense_variant	1/4	1	NM_001080998.2	A2
FRG2B	ENST00000443774.5	c.31C>T	p.His11Tyr	missense_variant	1/4	1		P4
	ENST00000655152.1	n.446-821G>A		intron_variant, non_coding_transcript_variant
	ENST00000669404.1	n.303-821G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

Alfa AF: 0.319 Hom.: 0

ExAC AF: 0.491 AC: 59617

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.8
DANN	Benign	0.90
DEOGEN2	Benign	0.081	.;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.53	T;T
MetaRNN	Benign	0.0023	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.97	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.51	T
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	T
GERP RS		0.11
Varity_R		0.18
gMVP		0.015

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

Other links and lift over

dbSNP: rs79777505; hg19: chr10-135440216; COSMIC: COSV71042480;