2-241373241-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014808.4(FARP2):​c.134A>G​(p.His45Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,548,986 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). 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 0.0013 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (41 hom.)
• Consequence: FARP2 NM_014808.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004382789).
• BP6: Variant 2-241373241-A-G is Benign according to our data. Variant chr2-241373241-A-G is described in ClinVar as Benign. ClinVar VariationId is 708286.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00126 (192/152314) while in subpopulation SAS AF = 0.0197 (95/4828). AF 95% confidence interval is 0.0165. There are 3 homozygotes in GnomAd4. There are 116 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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>G	p.His45Arg	missense	Exon 2 of 27	NP_055623.1	O94887-1
	FARP2	NM_001282983.2		c.134A>G	p.His45Arg	missense	Exon 2 of 18	NP_001269912.1	O94887-2
	FARP2	NM_001282984.2		c.134A>G	p.His45Arg	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>G	p.His45Arg	missense	Exon 2 of 27	ENSP00000264042.3	O94887-1
	FARP2	ENST00000373287.8	TSL:1	c.134A>G	p.His45Arg	missense	Exon 2 of 18	ENSP00000362384.4	O94887-2
	FARP2	ENST00000903053.1		c.134A>G	p.His45Arg	missense	Exon 2 of 28	ENSP00000573112.1

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 192 AN: 152196 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00283 AC: 624 AN: 220290 AF XY: 0.00355

Gnomad AFR exome AF: 0.0000672

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.00428

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000955

Gnomad NFE exome AF: 0.000882

Gnomad OTH exome AF: 0.00193

GnomAD4 exome AF: 0.00154 AC: 2145 AN: 1396672 Hom.: 41 Cov.: 32 AF XY: 0.00208 AC XY: 1432 AN XY: 689832

African (AFR) AF: 0.0000643 AC: 2 AN: 31108

American (AMR) AF: 0.000647 AC: 24 AN: 37112

Ashkenazi Jewish (ASJ) AF: 0.00399 AC: 97 AN: 24332

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37392

South Asian (SAS) AF: 0.0190 AC: 1493 AN: 78630

European-Finnish (FIN) AF: 0.0000382 AC: 2 AN: 52382

Middle Eastern (MID) AF: 0.00998 AC: 55 AN: 5510

European-Non Finnish (NFE) AF: 0.000331 AC: 355 AN: 1073104

Other (OTH) AF: 0.00203 AC: 116 AN: 57102

GnomAD4 genome AF: 0.00126 AC: 192 AN: 152314 Hom.: 3 Cov.: 32 AF XY: 0.00156 AC XY: 116 AN XY: 74486

African (AFR) AF: 0.000144 AC: 6 AN: 41578

American (AMR) AF: 0.000654 AC: 10 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68022

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00114 Hom.: 5

Bravo AF: 0.000657

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.00334 AC: 405

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	0.39
DANN	Benign	0.73
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.94	L
PhyloP100		-0.086
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.17
Sift	Benign	0.32	T
Sift4G	Benign	0.48	T
Polyphen		0.0010	B
Vest4		0.22
MVP		0.51
MPC		0.064
ClinPred		0.0085	T
GERP RS		-7.7
PromoterAI		0.018	Neutral
Varity_R		0.026
gMVP		0.17
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;