2-241431686-C-T

Position:

• chr2-241431686-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014808.4(FARP2):​c.779C>T​(p.Thr260Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0993 in 1,573,582 control chromosomes in the GnomAD database, including 8,274 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.10 (854 hom., cov: 32)
  • Exomes 𝑓: 0.099 (7420 hom.)
• Consequence: FARP2 NM_014808.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.99

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022568107).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FARP2	NM_014808.4	c.779C>T	p.Thr260Ile	missense_variant	9/27	ENST00000264042.8	NP_055623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FARP2	ENST00000264042.8	c.779C>T	p.Thr260Ile	missense_variant	9/27	1	NM_014808.4	ENSP00000264042.3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15344 AN: 152016 Hom.: 851 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0964

GnomAD3 exomes AF: 0.0932 AC: 22778 AN: 244304 Hom.: 1180 AF XY: 0.0926 AC XY: 12246 AN XY: 132260

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.0999

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.0178

Gnomad SAS exome AF: 0.0776

Gnomad FIN exome AF: 0.0730

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.0976

GnomAD4 exome AF: 0.0991 AC: 140869 AN: 1421448 Hom.: 7420 Cov.: 25 AF XY: 0.0992 AC XY: 70330 AN XY: 709198

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0970

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.0492

Gnomad4 SAS exome AF: 0.0764

Gnomad4 FIN exome AF: 0.0766

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.0960

GnomAD4 genome AF: 0.101 AC: 15360 AN: 152134 Hom.: 854 Cov.: 32 AF XY: 0.0980 AC XY: 7287 AN XY: 74358

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.0749

Gnomad4 FIN AF: 0.0681

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0954

Alfa AF: 0.104 Hom.: 2326

Bravo AF: 0.102

TwinsUK AF: 0.113 AC: 419

ALSPAC AF: 0.111 AC: 429

ESP6500AA AF: 0.0967 AC: 426

ESP6500EA AF: 0.112 AC: 961

ExAC AF: 0.0931 AC: 11306

Asia WGS AF: 0.0550 AC: 191 AN: 3478

EpiCase AF: 0.100

EpiControl AF: 0.102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;.;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D
MetaRNN	Benign	0.0023	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.3	D;.;D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0020	D;.;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.13
MPC		0.15
ClinPred		0.015	T
GERP RS		4.8
Varity_R		0.70
gMVP		0.39

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: rs757978; hg19: chr2-242371101;