rs1370497

Variant names:

• chr2-152607934-A-G
• rs1370497
• NM_052905.4:c.951+521A>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.951+521A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,722 control chromosomes in the GnomAD database, including 15,264 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 0.43 (15264 hom., cov: 31)
• Consequence: FMNL2 NM_052905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMNL2	NM_052905.4	c.951+521A>G		intron_variant	Intron 10 of 25	ENST00000288670.14	NP_443137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMNL2	ENST00000288670.14	c.951+521A>G		intron_variant	Intron 10 of 25	1	NM_052905.4	ENSP00000288670.9

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65338 AN: 151604 Hom.: 15260 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.431 AC: 65356 AN: 151722 Hom.: 15264 Cov.: 31 AF XY: 0.436 AC XY: 32311 AN XY: 74150

African (AFR) AF: 0.273 AC: 11294 AN: 41302

American (AMR) AF: 0.437 AC: 6670 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1727 AN: 3466

East Asian (EAS) AF: 0.824 AC: 4252 AN: 5158

South Asian (SAS) AF: 0.510 AC: 2444 AN: 4796

European-Finnish (FIN) AF: 0.496 AC: 5217 AN: 10508

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32321 AN: 67936

Other (OTH) AF: 0.453 AC: 949 AN: 2096

Alfa AF: 0.458 Hom.: 23345

Bravo AF: 0.422

Asia WGS AF: 0.640 AC: 2224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.021
DANN	Benign	0.26
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1370497; hg19: chr2-153464448; COSMIC: COSV107311217; COSMIC: COSV107311217;