rs4664114

Positions:

• chr2-152521945-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_052905.4(FMNL2):​c.120T>C​(p.Asn40=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,608,258 control chromosomes in the GnomAD database, including 370,392 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (34857 hom., cov: 31)
  • Exomes 𝑓: 0.68 (335535 hom.)
• Consequence: FMNL2 NM_052905.4 splice_region, synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.84

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 2-152521945-T-C is Benign according to our data. Variant chr2-152521945-T-C is described in ClinVar as [Benign]. Clinvar id is 1526376.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMNL2	NM_052905.4	c.120T>C	p.Asn40=	splice_region_variant, synonymous_variant	2/26	ENST00000288670.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMNL2	ENST00000288670.14	c.120T>C	p.Asn40=	splice_region_variant, synonymous_variant	2/26	1	NM_052905.4	P1
FMNL2	ENST00000475377.3	c.120T>C	p.Asn40=	splice_region_variant, synonymous_variant	2/28	5

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102587 AN: 151862 Hom.: 34836 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.661

GnomAD3 exomes AF: 0.694 AC: 171716 AN: 247598 Hom.: 60166 AF XY: 0.687 AC XY: 92238 AN XY: 134280

Gnomad AFR exome AF: 0.645

Gnomad AMR exome AF: 0.831

Gnomad ASJ exome AF: 0.603

Gnomad EAS exome AF: 0.738

Gnomad SAS exome AF: 0.681

Gnomad FIN exome AF: 0.705

Gnomad NFE exome AF: 0.661

Gnomad OTH exome AF: 0.681

GnomAD4 exome AF: 0.677 AC: 986407 AN: 1456278 Hom.: 335535 Cov.: 33 AF XY: 0.676 AC XY: 490171 AN XY: 724644

Gnomad4 AFR exome AF: 0.644

Gnomad4 AMR exome AF: 0.822

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.744

Gnomad4 SAS exome AF: 0.682

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.671

Gnomad4 OTH exome AF: 0.670

GnomAD4 genome AF: 0.675 AC: 102648 AN: 151980 Hom.: 34857 Cov.: 31 AF XY: 0.678 AC XY: 50317 AN XY: 74242

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.655

Alfa AF: 0.667 Hom.: 44726

Bravo AF: 0.677

Asia WGS AF: 0.682 AC: 2376 AN: 3478

EpiCase AF: 0.658

EpiControl AF: 0.666

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 22, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs4664114; hg19: chr2-153378459; COSMIC: COSV56491305;