2-241373241-A-T

Variant names:

• chr2-241373241-A-T
• rs150312458
• NM_014808.4:c.134A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014808.4(FARP2):​c.134A>T​(p.His45Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: FARP2 NM_014808.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 6 publications found

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

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=0.14772525).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP2	NM_014808.4	MANE Select	c.134A>T	p.His45Leu	missense	Exon 2 of 27	NP_055623.1	O94887-1
	FARP2	NM_001282983.2		c.134A>T	p.His45Leu	missense	Exon 2 of 18	NP_001269912.1	O94887-2
	FARP2	NM_001282984.2		c.134A>T	p.His45Leu	missense	Exon 2 of 18	NP_001269913.1	O94887-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP2	ENST00000264042.8	TSL:1 MANE Select	c.134A>T	p.His45Leu	missense	Exon 2 of 27	ENSP00000264042.3	O94887-1
	FARP2	ENST00000373287.8	TSL:1	c.134A>T	p.His45Leu	missense	Exon 2 of 18	ENSP00000362384.4	O94887-2
	FARP2	ENST00000903053.1		c.134A>T	p.His45Leu	missense	Exon 2 of 28	ENSP00000573112.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000454 AC: 1 AN: 220290 AF XY: 0.00

Gnomad AFR exome AF: 0.0000672

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.0000724 AC: 3 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 5

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	1.1
DANN	Benign	0.64
DEOGEN2	Benign	0.075	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.94	L
PhyloP100		-0.086
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.32
Sift	Benign	0.16	T
Sift4G	Benign	0.71	T
Polyphen		0.094	B
Vest4		0.30
MutPred		0.39		Loss of disorder (P = 0.0662)
MVP		0.50
MPC		0.065
ClinPred		0.63	D
GERP RS		-7.7
PromoterAI		-0.031	Neutral
Varity_R		0.053
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs150312458; hg19: chr2-242312656;