2-152558730-T-TTTC

Variant names:

• chr2-152558730-T-TTTC
• rs1553476567
• NM_052905.4:c.360-10_360-9insTTC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_052905.4(FMNL2):​c.360-10_360-9insTTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000979 in 1,562,736 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: FMNL2 NM_052905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMNL2	NM_052905.4	c.360-10_360-9insTTC		intron_variant	Intron 4 of 25	ENST00000288670.14	NP_443137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMNL2	ENST00000288670.14	c.360-10_360-9insTTC		intron_variant	Intron 4 of 25	1	NM_052905.4	ENSP00000288670.9

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150720 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000206 AC: 44 AN: 213212 AF XY: 0.000224

Gnomad AFR exome AF: 0.000732

Gnomad AMR exome AF: 0.000404

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000108

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.000773

GnomAD4 exome AF: 0.000106 AC: 150 AN: 1412016 Hom.: 0 Cov.: 34 AF XY: 0.000101 AC XY: 71 AN XY: 702778

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000531 AC: 17 AN: 31992

American (AMR) AF: 0.000358 AC: 15 AN: 41876

Ashkenazi Jewish (ASJ) AF: 0.0000390 AC: 1 AN: 25612

East Asian (EAS) AF: 0.00 AC: 0 AN: 39020

South Asian (SAS) AF: 0.0000241 AC: 2 AN: 82912

European-Finnish (FIN) AF: 0.0000788 AC: 4 AN: 50776

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5644

European-Non Finnish (NFE) AF: 0.0000976 AC: 105 AN: 1075710

Other (OTH) AF: 0.0000855 AC: 5 AN: 58474

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150720 Hom.: 0 Cov.: 21 AF XY: 0.0000408 AC XY: 3 AN XY: 73452

African (AFR) AF: 0.00 AC: 0 AN: 40812

American (AMR) AF: 0.000132 AC: 2 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67820

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553476567; hg19: chr2-153415244;