17-7593064-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004860.4(FXR2):c.1448G>A(p.Arg483Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00332 in 1,587,458 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (13 hom.)
• Consequence: FXR2 NM_004860.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.18

Genes affected

FXR2 (HGNC:4024): (FMR1 autosomal homolog 2) The protein encoded by this gene is a RNA binding protein containing two KH domains and one RCG box, which is similar to FMRP and FXR1. It associates with polyribosomes, predominantly with 60S large ribosomal subunits. This encoded protein may self-associate or interact with FMRP and FXR1. It may have a role in the development of fragile X cognitive disability syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012820035).
• BP6: Variant 17-7593064-C-T is Benign according to our data. Variant chr17-7593064-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779453.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 266 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXR2	NM_004860.4	c.1448G>A	p.Arg483Gln	missense_variant	13/17	ENST00000250113.12
FXR2	XM_047437106.1	c.1448G>A	p.Arg483Gln	missense_variant	13/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXR2	ENST00000250113.12	c.1448G>A	p.Arg483Gln	missense_variant	13/17	1	NM_004860.4	P1
FXR2	ENST00000704984.1	c.1667G>A	p.Arg556Gln	missense_variant	13/17

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 266 AN: 152132 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00187 AC: 415 AN: 221564 Hom.: 1 AF XY: 0.00186 AC XY: 225 AN XY: 121168

Gnomad AFR exome AF: 0.000553

Gnomad AMR exome AF: 0.000211

Gnomad ASJ exome AF: 0.000249

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00189

Gnomad FIN exome AF: 0.000342

Gnomad NFE exome AF: 0.00332

Gnomad OTH exome AF: 0.000566

GnomAD4 exome AF: 0.00349 AC: 5005 AN: 1435208 Hom.: 13 Cov.: 32 AF XY: 0.00342 AC XY: 2436 AN XY: 713254

Gnomad4 AFR exome AF: 0.000627

Gnomad4 AMR exome AF: 0.000235

Gnomad4 ASJ exome AF: 0.000245

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00210

Gnomad4 FIN exome AF: 0.000532

Gnomad4 NFE exome AF: 0.00419

Gnomad4 OTH exome AF: 0.00257

GnomAD4 genome AF: 0.00175 AC: 267 AN: 152250 Hom.: 1 Cov.: 32 AF XY: 0.00157 AC XY: 117 AN XY: 74426

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00316

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00298 Hom.: 1

Bravo AF: 0.00180

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.00110 AC: 4

ESP6500EA AF: 0.00381 AC: 31

ExAC AF: 0.00205 AC: 247

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.65	N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.33	T
Polyphen		1.0	D
Vest4		0.27
MVP		0.49
MPC		1.0
ClinPred		0.020	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.49

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: rs201194889; hg19: chr17-7496382; COSMIC: COSV51468395; COSMIC: COSV51468395;