Variant chr2-241373240-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014808.4(FARP2):c.133C>T(p.His45Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,553,528 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H45R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0038 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 35 hom. )

Consequence

FARP2
NM_014808.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.42

Variant links:

Genes affected

FARP2 (HGNC:16460): (FERM, ARH/RhoGEF and pleckstrin domain protein 2) Enables guanyl-nucleotide exchange factor activity. Acts upstream of or within Rac protein signal transduction and neuron remodeling. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FARP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005847752).

BP6

Variant 2-241373240-C-T is Benign according to our data. Variant chr2-241373240-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 770881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARP2	NM_014808.4 linkuse as main transcript	c.133C>T	p.His45Tyr	missense_variant	2/27	ENST00000264042.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP2	ENST00000264042.8 linkuse as main transcript	c.133C>T	p.His45Tyr	missense_variant	2/27	1	NM_014808.4	P1	O94887-1

Frequencies

GnomAD3 genomes

AF:

0.00382

AC:

581

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00662

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00361

AC:

811

AN:

224444

Hom.:

AF XY:

0.00373

AC XY:

455

AN XY:

122072

show subpopulations

Gnomad AFR exome

AF:

0.000935

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00324

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000585

Gnomad FIN exome

AF:

0.00280

Gnomad NFE exome

AF:

0.00605

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00644

AC:

9020

AN:

1401260

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

4266

AN XY:

692480

show subpopulations

Gnomad4 AFR exome

AF:

0.00121

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00334

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000479

Gnomad4 FIN exome

AF:

0.00255

Gnomad4 NFE exome

AF:

0.00778

Gnomad4 OTH exome

AF:

0.00499

GnomAD4 genome

AF:

0.00382

AC:

581

AN:

152268

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

265

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00662

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00607

Hom.:

Bravo

AF:

0.00393

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.00339

AC:

412

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	FARP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.36

DEOGEN2

Benign

0.081

T;.;.;T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.74

T;T;T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0058

T;T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.8

L;L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

N;.;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.088

T;.;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.010

B;.;B;.;.

Vest4

0.27

MVP

0.82

MPC

0.063

ClinPred

0.011

GERP RS

2.3

Varity_R

0.053

gMVP

0.12

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