2-241373128-A-G

Variant names:

• chr2-241373128-A-G
• rs139981990
• NM_014808.4:c.21A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014808.4(FARP2):​c.21A>G​(p.Thr7Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 1,294,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T7T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: FARP2 NM_014808.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.43
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-4.43 with no splicing effect.

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.21A>G	p.Thr7Thr	synonymous	Exon 2 of 27	NP_055623.1	O94887-1
	FARP2	NM_001282983.2		c.21A>G	p.Thr7Thr	synonymous	Exon 2 of 18	NP_001269912.1	O94887-2
	FARP2	NM_001282984.2		c.21A>G	p.Thr7Thr	synonymous	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.21A>G	p.Thr7Thr	synonymous	Exon 2 of 27	ENSP00000264042.3	O94887-1
	FARP2	ENST00000373287.8	TSL:1	c.21A>G	p.Thr7Thr	synonymous	Exon 2 of 18	ENSP00000362384.4	O94887-2
	FARP2	ENST00000903053.1		c.21A>G	p.Thr7Thr	synonymous	Exon 2 of 28	ENSP00000573112.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000155 AC: 2 AN: 1294134 Hom.: 0 Cov.: 32 AF XY: 0.00000157 AC XY: 1 AN XY: 635882

⚠️ 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: 27686

American (AMR) AF: 0.00 AC: 0 AN: 25820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20468

East Asian (EAS) AF: 0.00 AC: 0 AN: 33508

South Asian (SAS) AF: 0.00 AC: 0 AN: 63394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5020

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1017700

Other (OTH) AF: 0.00 AC: 0 AN: 51788

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), 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
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.57
PhyloP100		-4.4
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs139981990; hg19: chr2-242312543;