2-241373128-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014808.4(FARP2):​c.21A>C​(p.Thr7Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,445,912 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (11 hom.)
• Consequence: FARP2 NM_014808.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-241373128-A-C is Benign according to our data. Variant chr2-241373128-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 718858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.43 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 11 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.21A>C	p.Thr7Thr	synonymous	Exon 2 of 27	NP_055623.1	O94887-1
	FARP2	NM_001282983.2		c.21A>C	p.Thr7Thr	synonymous	Exon 2 of 18	NP_001269912.1	O94887-2
	FARP2	NM_001282984.2		c.21A>C	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>C	p.Thr7Thr	synonymous	Exon 2 of 27	ENSP00000264042.3	O94887-1
	FARP2	ENST00000373287.8	TSL:1	c.21A>C	p.Thr7Thr	synonymous	Exon 2 of 18	ENSP00000362384.4	O94887-2
	FARP2	ENST00000903053.1		c.21A>C	p.Thr7Thr	synonymous	Exon 2 of 28	ENSP00000573112.1

Frequencies

GnomAD3 genomes AF: 0.00125 AC: 190 AN: 151682 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000286

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00219

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00184 AC: 331 AN: 179668 AF XY: 0.00182

Gnomad AFR exome AF: 0.000480

Gnomad AMR exome AF: 0.000938

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000459

Gnomad NFE exome AF: 0.00264

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00236 AC: 3060 AN: 1294118 Hom.: 11 Cov.: 32 AF XY: 0.00233 AC XY: 1484 AN XY: 635874

African (AFR) AF: 0.000470 AC: 13 AN: 27686

American (AMR) AF: 0.000658 AC: 17 AN: 25818

Ashkenazi Jewish (ASJ) AF: 0.0000489 AC: 1 AN: 20468

East Asian (EAS) AF: 0.0000298 AC: 1 AN: 33508

South Asian (SAS) AF: 0.00297 AC: 188 AN: 63392

European-Finnish (FIN) AF: 0.000800 AC: 39 AN: 48750

Middle Eastern (MID) AF: 0.000797 AC: 4 AN: 5020

European-Non Finnish (NFE) AF: 0.00267 AC: 2719 AN: 1017690

Other (OTH) AF: 0.00151 AC: 78 AN: 51786

GnomAD4 genome AF: 0.00125 AC: 190 AN: 151794 Hom.: 1 Cov.: 32 AF XY: 0.00115 AC XY: 85 AN XY: 74172

African (AFR) AF: 0.000338 AC: 14 AN: 41390

American (AMR) AF: 0.000655 AC: 10 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00229 AC: 11 AN: 4812

European-Finnish (FIN) AF: 0.000286 AC: 3 AN: 10490

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00219 AC: 149 AN: 67938

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00197 Hom.: 2

Bravo AF: 0.00127

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.98
DANN	Benign	0.57
PhyloP100		-4.4
PromoterAI		-0.0028	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; COSMIC: COSV50885509; COSMIC: COSV50885509;