chr2-241413302-C-A

Variant names:

• chr2-241413302-C-A
• rs145651106
• NM_014808.4:c.509-5C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014808.4(FARP2):​c.509-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,423,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FARP2 NM_014808.4 splice_region, intron
• Scores: Splicing: ADA: 0.002652
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).

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.509-5C>A		splice_region intron	N/A	NP_055623.1	O94887-1
	FARP2	NM_001282983.2		c.509-5C>A		splice_region intron	N/A	NP_001269912.1	O94887-2
	FARP2	NM_001282984.2		c.509-5C>A		splice_region intron	N/A	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.509-5C>A		splice_region intron	N/A	ENSP00000264042.3	O94887-1
	FARP2	ENST00000373287.8	TSL:1	c.509-5C>A		splice_region intron	N/A	ENSP00000362384.4	O94887-2
	FARP2	ENST00000903053.1		c.509-5C>A		splice_region intron	N/A	ENSP00000573112.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1423472 Hom.: 0 Cov.: 27 AF XY: 0.00000141 AC XY: 1 AN XY: 707494

⚠️ 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: 32788

American (AMR) AF: 0.00 AC: 0 AN: 42392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25508

East Asian (EAS) AF: 0.00 AC: 0 AN: 39346

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52414

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083698

Other (OTH) AF: 0.00 AC: 0 AN: 59106

⚠️ 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
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		-0.038

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0027
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.010		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: rs145651106; hg19: chr2-242352717;