Variant 2-241373241-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014808.4(FARP2):c.134A>G(p.His45Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,548,986 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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. H45Y) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0013 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 41 hom. )

Consequence

FARP2
NM_014808.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0860

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004382789).

BP6

Variant 2-241373241-A-G is Benign according to our data. Variant chr2-241373241-A-G is described in ClinVar as [Benign]. Clinvar id is 708286.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00126 (192/152314) while in subpopulation SAS AF= 0.0197 (95/4828). AF 95% confidence interval is 0.0165. There are 3 homozygotes in gnomad4. There are 116 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARP2	NM_014808.4 linkuse as main transcript	c.134A>G	p.His45Arg	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.134A>G	p.His45Arg	missense_variant	2/27	1	NM_014808.4	P1	O94887-1

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

192

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00283

AC:

624

AN:

220290

Hom.:

AF XY:

0.00355

AC XY:

426

AN XY:

119836

show subpopulations

Gnomad AFR exome

AF:

0.0000672

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0188

Gnomad FIN exome

AF:

0.0000955

Gnomad NFE exome

AF:

0.000882

Gnomad OTH exome

AF:

0.00193

GnomAD4 exome

AF:

0.00154

AC:

2145

AN:

1396672

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

1432

AN XY:

689832

show subpopulations

Gnomad4 AFR exome

AF:

0.0000643

Gnomad4 AMR exome

AF:

0.000647

Gnomad4 ASJ exome

AF:

0.00399

Gnomad4 EAS exome

AF:

0.0000267

Gnomad4 SAS exome

AF:

0.0190

Gnomad4 FIN exome

AF:

0.0000382

Gnomad4 NFE exome

AF:

0.000331

Gnomad4 OTH exome

AF:

0.00203

GnomAD4 genome

AF:

0.00126

AC:

192

AN:

152314

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000657

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00334

AC:

405

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.25

CADD

Benign

0.39

DANN

Benign

0.73

DEOGEN2

Benign

0.053

T;.;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.55

T;T;T;T;T

MetaRNN

Benign

0.0044

T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.94

L;L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.5

N;.;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.32

T;.;T;T;T

Sift4G

Benign

0.48

T;T;T;T;T

Polyphen

0.0010

B;.;B;.;.

Vest4

0.22

MVP

0.51

MPC

0.064

ClinPred

0.0085

GERP RS

-7.7

Varity_R

0.026

gMVP

0.17

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