2-241373240-C-T

Variant names:

• chr2-241373240-C-T
• rs61739735
• NM_014808.4:c.133C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014808.4(FARP2):​c.133C>T​(p.His45Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,553,528 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H45R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0038 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (35 hom.)
• Consequence: FARP2 NM_014808.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.42
• Publications: 11 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005847752).
• BP6: Variant 2-241373240-C-T is Benign according to our data. Variant chr2-241373240-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 770881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 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.133C>T	p.His45Tyr	missense	Exon 2 of 27	NP_055623.1	O94887-1
	FARP2	NM_001282983.2		c.133C>T	p.His45Tyr	missense	Exon 2 of 18	NP_001269912.1	O94887-2
	FARP2	NM_001282984.2		c.133C>T	p.His45Tyr	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.133C>T	p.His45Tyr	missense	Exon 2 of 27	ENSP00000264042.3	O94887-1
	FARP2	ENST00000373287.8	TSL:1	c.133C>T	p.His45Tyr	missense	Exon 2 of 18	ENSP00000362384.4	O94887-2
	FARP2	ENST00000903053.1		c.133C>T	p.His45Tyr	missense	Exon 2 of 28	ENSP00000573112.1

Frequencies

GnomAD3 genomes AF: 0.00382 AC: 581 AN: 152148 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00662

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00361 AC: 811 AN: 224444 AF XY: 0.00373

Gnomad AFR exome AF: 0.000935

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00324

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00280

Gnomad NFE exome AF: 0.00605

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00644 AC: 9020 AN: 1401260 Hom.: 35 Cov.: 32 AF XY: 0.00616 AC XY: 4266 AN XY: 692480

African (AFR) AF: 0.00121 AC: 38 AN: 31330

American (AMR) AF: 0.00159 AC: 61 AN: 38310

Ashkenazi Jewish (ASJ) AF: 0.00334 AC: 82 AN: 24522

East Asian (EAS) AF: 0.00 AC: 0 AN: 37450

South Asian (SAS) AF: 0.000479 AC: 38 AN: 79258

European-Finnish (FIN) AF: 0.00255 AC: 134 AN: 52480

Middle Eastern (MID) AF: 0.00217 AC: 12 AN: 5530

European-Non Finnish (NFE) AF: 0.00778 AC: 8369 AN: 1075056

Other (OTH) AF: 0.00499 AC: 286 AN: 57324

GnomAD4 genome AF: 0.00382 AC: 581 AN: 152268 Hom.: 5 Cov.: 32 AF XY: 0.00356 AC XY: 265 AN XY: 74460

African (AFR) AF: 0.00128 AC: 53 AN: 41554

American (AMR) AF: 0.00235 AC: 36 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00662 AC: 450 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00574 Hom.: 4

Bravo AF: 0.00393

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00856 AC: 33

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00616 AC: 53

ExAC AF: 0.00339 AC: 412

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.36
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.088	T
Sift4G	Benign	1.0	T
Polyphen		0.010	B
Vest4		0.27
MVP		0.82
MPC		0.063
ClinPred		0.011	T
GERP RS		2.3
PromoterAI		-0.00040	Neutral
Varity_R		0.053
gMVP		0.12
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: rs61739735; hg19: chr2-242312655; COSMIC: COSV99055041;