chr2-241403930-T-A

Position:

• chr2-241403930-T-A

Variant summary

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

The NM_014808.4(FARP2):​c.286T>A​(p.Trp96Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FARP2 NM_014808.4 missense, splice_region
• Scores: Splicing: ADA: 0.001001
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19

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, 0.746

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARP2	NM_014808.4	c.286T>A	p.Trp96Arg	missense_variant, splice_region_variant	3/27	ENST00000264042.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP2	ENST00000264042.8	c.286T>A	p.Trp96Arg	missense_variant, splice_region_variant	3/27	1	NM_014808.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.286T>A (p.W96R) alteration is located in exon 3 (coding exon 2) of the FARP2 gene. This alteration results from a T to A substitution at nucleotide position 286, causing the tryptophan (W) at amino acid position 96 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Benign	0.92
DEOGEN2	Benign	0.38	T;.;.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.72	T;T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.90	L;L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.7	D;.;D;D
REVEL	Uncertain	0.56
Sift	Benign	0.080	T;.;T;T
Sift4G	Benign	0.44	T;T;T;T
Polyphen		1.0	D;.;D;.
Vest4		0.87
MutPred		0.52		Gain of MoRF binding (P = 0.0373);Gain of MoRF binding (P = 0.0373);Gain of MoRF binding (P = 0.0373);Gain of MoRF binding (P = 0.0373);
MVP		0.66
MPC		0.46
ClinPred		0.90	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0010
dbscSNV1_RF	Benign	0.030
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-242343345;