rs10497106

chr2-152553314-A-Gchr2-152553314-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052905.4(FMNL2):c.359+4217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,030 control chromosomes in the GnomAD database, including 4,865 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 0.23 (4865 hom., cov: 32)
• Consequence: FMNL2 NM_052905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMNL2	NM_052905.4	c.359+4217A>G		intron_variant		ENST00000288670.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMNL2	ENST00000288670.14	c.359+4217A>G		intron_variant		1	NM_052905.4	P1
FMNL2	ENST00000475377.3	c.359+4217A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34549 AN: 151912 Hom.: 4857 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.228 AC: 34595 AN: 152030 Hom.: 4865 Cov.: 32 AF XY: 0.225 AC XY: 16719 AN XY: 74320

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.221

Alfa AF: 0.171 Hom.: 4681

Bravo AF: 0.235

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	2.1
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs10497106; hg19: chr2-153409828;