Variant chr12-69574312-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000549921.6(FRS2):c.884G>A(p.Arg295Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,782 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: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

FRS2
ENST00000549921.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

Variant links:

Genes affected

FRS2 (HGNC:16971): (fibroblast growth factor receptor substrate 2) Enables fibroblast growth factor receptor binding activity and neurotrophin TRKA receptor binding activity. Involved in negative regulation of cardiac muscle cell differentiation. Acts upstream of or within fibroblast growth factor receptor signaling pathway. Located in adherens junction. Biomarker of renal cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

FRS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2430945).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRS2	NM_001278356.2 linkuse as main transcript	c.884G>A	p.Arg295Gln	missense_variant	9/9	ENST00000549921.6	NP_001265285.1	Q8WU20L7RTG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FRS2	ENST00000549921.6 linkuse as main transcript	c.884G>A	p.Arg295Gln	missense_variant	9/9	1	NM_001278356.2	ENSP00000450048.1	Q8WU20
FRS2	ENST00000550389.5 linkuse as main transcript	c.884G>A	p.Arg295Gln	missense_variant	7/7	1		ENSP00000447241.1	Q8WU20
FRS2	ENST00000397997.6 linkuse as main transcript	c.884G>A	p.Arg295Gln	missense_variant	7/7	5		ENSP00000381083.2	Q8WU20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249456

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

The c.884G>A (p.R295Q) alteration is located in exon 10 (coding exon 5) of the FRS2 gene. This alteration results from a G to A substitution at nucleotide position 884, causing the arginine (R) at amino acid position 295 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.40

T;T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;.;D

M_CAP

Benign

0.0087

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.080

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.53

T;T;T

Polyphen

0.97

D;D;D

Vest4

0.25

MutPred

0.27

Loss of phosphorylation at S292 (P = 0.0977);Loss of phosphorylation at S292 (P = 0.0977);Loss of phosphorylation at S292 (P = 0.0977);

MVP

0.69

ClinPred

0.48

GERP RS

5.4

Varity_R

0.15

gMVP

0.16

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