rs757978

Variant names:

• chr2-241431686-C-A
• rs757978
• NM_014808.4:c.779C>A
• FARP2 p.Thr260Asn

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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.

• 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
• Publications: 83 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 3 ACMG points.

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

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.779C>A	p.Thr260Asn	missense	Exon 9 of 27	NP_055623.1	O94887-1
	FARP2	NM_001282983.2		c.779C>A	p.Thr260Asn	missense	Exon 9 of 18	NP_001269912.1	O94887-2
	FARP2	NM_001282984.2		c.779C>A	p.Thr260Asn	missense	Exon 9 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.779C>A	p.Thr260Asn	missense	Exon 9 of 27	ENSP00000264042.3	O94887-1
	FARP2	ENST00000373287.8	TSL:1	c.779C>A	p.Thr260Asn	missense	Exon 9 of 18	ENSP00000362384.4	O94887-2
	FARP2	ENST00000903053.1		c.779C>A	p.Thr260Asn	missense	Exon 9 of 28	ENSP00000573112.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244304 AF XY: 0.00000756

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32402

American (AMR) AF: 0.00 AC: 0 AN: 43126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25792

East Asian (EAS) AF: 0.00 AC: 0 AN: 39162

South Asian (SAS) AF: 0.00 AC: 0 AN: 84234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1083096

Other (OTH) AF: 0.00 AC: 0 AN: 59112

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.091	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.011	D
Varity_R		0.56
gMVP		0.38
Mutation Taster		=59/41	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs757978;

hg19: chr2-242371101;