2-152617280-T-G

Variant names:

• chr2-152617280-T-G
• rs2304556
• NM_052905.4:c.1314+88T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052905.4(FMNL2):​c.1314+88T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,145,242 control chromosomes in the GnomAD database, including 62,920 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10186 hom., cov: 32)
  • Exomes 𝑓: 0.32 (52734 hom.)
• Consequence: FMNL2 NM_052905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 14 publications found

Genes affected

FMNL2 (HGNC:18267): (formin like 2) This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. Alternatively spliced transcript variants encoding different isoforms have been described but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMNL2	NM_052905.4	c.1314+88T>G		intron_variant	Intron 13 of 25	ENST00000288670.14	NP_443137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMNL2	ENST00000288670.14	c.1314+88T>G		intron_variant	Intron 13 of 25	1	NM_052905.4	ENSP00000288670.9

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54191 AN: 152006 Hom.: 10154 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.321 AC: 318831 AN: 993118 Hom.: 52734 AF XY: 0.325 AC XY: 164935 AN XY: 507744

African (AFR) AF: 0.466 AC: 10813 AN: 23204

American (AMR) AF: 0.391 AC: 12502 AN: 31986

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 9116 AN: 20408

East Asian (EAS) AF: 0.310 AC: 11472 AN: 36962

South Asian (SAS) AF: 0.424 AC: 29303 AN: 69158

European-Finnish (FIN) AF: 0.221 AC: 11341 AN: 51244

Middle Eastern (MID) AF: 0.419 AC: 1988 AN: 4744

European-Non Finnish (NFE) AF: 0.306 AC: 217308 AN: 710952

Other (OTH) AF: 0.337 AC: 14988 AN: 44460

GnomAD4 genome AF: 0.357 AC: 54277 AN: 152124 Hom.: 10186 Cov.: 32 AF XY: 0.355 AC XY: 26416 AN XY: 74384

African (AFR) AF: 0.452 AC: 18744 AN: 41474

American (AMR) AF: 0.396 AC: 6060 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1580 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1472 AN: 5162

South Asian (SAS) AF: 0.423 AC: 2040 AN: 4824

European-Finnish (FIN) AF: 0.208 AC: 2208 AN: 10596

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20888 AN: 67986

Other (OTH) AF: 0.403 AC: 850 AN: 2108

Alfa AF: 0.328 Hom.: 14130

Bravo AF: 0.372

Asia WGS AF: 0.418 AC: 1453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		0.093
Mutation Taster		=100/0	polymorphism (auto)

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: rs2304556; hg19: chr2-153473794; COSMIC: COSV56495959; COSMIC: COSV56495959;