2-152582077-G-C

Variant names:

• chr2-152582077-G-C
• rs10497109
• NM_052905.4:c.876+1028G>C

Variant summary

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

The NM_052905.4(FMNL2):​c.876+1028G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 152,204 control chromosomes in the GnomAD database, including 231 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 0.042 (231 hom., cov: 32)
• Consequence: FMNL2 NM_052905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMNL2	NM_052905.4	c.876+1028G>C		intron_variant	Intron 9 of 25	ENST00000288670.14	NP_443137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMNL2	ENST00000288670.14	c.876+1028G>C		intron_variant	Intron 9 of 25	1	NM_052905.4	ENSP00000288670.9

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6381 AN: 152086 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.00905

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0321

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

GnomAD4 genome AF: 0.0419 AC: 6380 AN: 152204 Hom.: 231 Cov.: 32 AF XY: 0.0428 AC XY: 3183 AN XY: 74424

African (AFR) AF: 0.00903 AC: 375 AN: 41540

American (AMR) AF: 0.0273 AC: 417 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0127 AC: 61 AN: 4822

European-Finnish (FIN) AF: 0.116 AC: 1227 AN: 10576

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0591 AC: 4019 AN: 67998

Other (OTH) AF: 0.0318 AC: 67 AN: 2110

Alfa AF: 0.0329 Hom.: 35

Bravo AF: 0.0337

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.49
PhyloP100		0.043
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: rs10497109; hg19: chr2-153438591;