rs757978

Positions:

• chr2-241431686-C-A
• chr2-241431686-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014808.4(FARP2):​c.779C>A​(p.Thr260Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,425,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T260I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARP2	NM_014808.4	c.779C>A	p.Thr260Asn	missense_variant	9/27	ENST00000264042.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP2	ENST00000264042.8	c.779C>A	p.Thr260Asn	missense_variant	9/27	1	NM_014808.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244304 Hom.: 0 AF XY: 0.00000756 AC XY: 1 AN XY: 132260

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425784 Hom.: 0 Cov.: 25 AF XY: 0.00000141 AC XY: 1 AN XY: 711164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Uncertain	2.1	M;M;M
MutationTaster	Benign	1.0e-7	P;P;P
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.4	D;.;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.013	D;.;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.62
MutPred		0.42		Gain of relative solvent accessibility (P = 0.0999);Gain of relative solvent accessibility (P = 0.0999);Gain of relative solvent accessibility (P = 0.0999);
MVP		0.87
MPC		0.37
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.56
gMVP		0.38

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;