2-152558730-T-TTTTTC

Variant names:

• chr2-152558730-T-TTTTTC
• rs1553476567
• NM_052905.4:c.360-10_360-9insTTTTC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_052905.4(FMNL2):​c.360-10_360-9insTTTTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000779 in 1,412,274 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: not found (cov: 21)
  • Exomes 𝑓: 0.0000078 (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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052905.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL2	NM_052905.4	MANE Select	c.360-10_360-9insTTTTC		intron	N/A	NP_443137.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL2	ENST00000288670.14	TSL:1 MANE Select	c.360-10_360-9insTTTTC		intron	N/A	ENSP00000288670.9	Q96PY5-3
	FMNL2	ENST00000475377.3	TSL:5	c.360-10_360-9insTTTTC		intron	N/A	ENSP00000418959.3	C9IZY8
	FMNL2	ENST00000850952.1		c.360-10_360-9insTTTTC		intron	N/A	ENSP00000521036.1	A0ABJ7H8L6

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000779 AC: 11 AN: 1412274 Hom.: 0 Cov.: 34 AF XY: 0.00000569 AC XY: 4 AN XY: 702906

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

African (AFR) AF: 0.00 AC: 0 AN: 32018

American (AMR) AF: 0.00 AC: 0 AN: 41886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25616

East Asian (EAS) AF: 0.00 AC: 0 AN: 39028

South Asian (SAS) AF: 0.00 AC: 0 AN: 82920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1075884

Other (OTH) AF: 0.00 AC: 0 AN: 58494

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000198006), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;