Genetic Variant FARP2:p.His45Asp (chr2-241373240-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014808.4(FARP2):c.133C>G(p.His45Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

FARP2
NM_014808.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.42

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15179929).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014808.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FARP2	NM_014808.4	MANE Select	c.133C>G	p.His45Asp	missense	Exon 2 of 27	NP_055623.1	O94887-1
FARP2	NM_001282983.2		c.133C>G	p.His45Asp	missense	Exon 2 of 18	NP_001269912.1	O94887-2
FARP2	NM_001282984.2		c.133C>G	p.His45Asp	missense	Exon 2 of 18	NP_001269913.1	O94887-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FARP2	ENST00000264042.8	TSL:1 MANE Select	c.133C>G	p.His45Asp	missense	Exon 2 of 27	ENSP00000264042.3	O94887-1
FARP2	ENST00000373287.8	TSL:1	c.133C>G	p.His45Asp	missense	Exon 2 of 18	ENSP00000362384.4	O94887-2
FARP2	ENST00000903053.1		c.133C>G	p.His45Asp	missense	Exon 2 of 28	ENSP00000573112.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1401292

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692494

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31330

American (AMR)

AF:

0.00

AC:

AN:

38310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24522

East Asian (EAS)

AF:

0.00

AC:

AN:

37450

South Asian (SAS)

AF:

0.00

AC:

AN:

79258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5530

European-Non Finnish (NFE)

AF:

9.30e-7

AC:

AN:

1075088

Other (OTH)

AF:

0.00

AC:

AN:

57324

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.056

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.66

M_CAP

Benign

0.023

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.0

PhyloP100

2.4

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.32

Sift

Benign

0.23

Sift4G

Benign

0.35

Polyphen

0.094

Vest4

0.46

MutPred

0.35

Gain of ubiquitination at K42 (P = 0.041)

MVP

0.80

MPC

0.079

ClinPred

0.11

GERP RS

2.3

PromoterAI

0.017

Neutral

(source)

Varity_R

0.091

gMVP

0.27

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over