2-152558730-T-TTC

Variant names:

• chr2-152558730-T-TTC
• rs1553476567
• NM_052905.4:c.360-10_360-9insTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_052905.4(FMNL2):​c.360-10_360-9insTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,558,688 control chromosomes in the GnomAD database, including 24 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0089 (19 hom., cov: 21)
  • Exomes 𝑓: 0.0030 (5 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00894 (1348/150802) while in subpopulation AFR AF = 0.0299 (1224/40914). AF 95% confidence interval is 0.0285. There are 19 homozygotes in GnomAd4. There are 669 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 gene

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_360-9insTC		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_360-9insTC		intron	N/A	ENSP00000288670.9	Q96PY5-3
	FMNL2	ENST00000475377.3	TSL:5	c.360-10_360-9insTC		intron	N/A	ENSP00000418959.3	C9IZY8
	FMNL2	ENST00000850952.1		c.360-10_360-9insTC		intron	N/A	ENSP00000521036.1	A0ABJ7H8L6

Frequencies

GnomAD3 genomes AF: 0.00888 AC: 1338 AN: 150692 Hom.: 19 Cov.: 21

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00567

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000292

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.00635

GnomAD2 exomes AF: 0.00343 AC: 731 AN: 213212 AF XY: 0.00300

Gnomad AFR exome AF: 0.0229

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.000875

Gnomad EAS exome AF: 0.00294

Gnomad FIN exome AF: 0.00205

Gnomad NFE exome AF: 0.00200

Gnomad OTH exome AF: 0.00367

GnomAD4 exome AF: 0.00297 AC: 4176 AN: 1407886 Hom.: 5 Cov.: 34 AF XY: 0.00275 AC XY: 1930 AN XY: 700760

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

African (AFR) AF: 0.0327 AC: 1035 AN: 31666

American (AMR) AF: 0.00357 AC: 149 AN: 41776

Ashkenazi Jewish (ASJ) AF: 0.000899 AC: 23 AN: 25592

East Asian (EAS) AF: 0.00211 AC: 82 AN: 38888

South Asian (SAS) AF: 0.00163 AC: 135 AN: 82718

European-Finnish (FIN) AF: 0.00156 AC: 79 AN: 50642

Middle Eastern (MID) AF: 0.00391 AC: 22 AN: 5622

European-Non Finnish (NFE) AF: 0.00227 AC: 2439 AN: 1072692

Other (OTH) AF: 0.00364 AC: 212 AN: 58290

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00894 AC: 1348 AN: 150802 Hom.: 19 Cov.: 21 AF XY: 0.00910 AC XY: 669 AN XY: 73556

African (AFR) AF: 0.0299 AC: 1224 AN: 40914

American (AMR) AF: 0.00573 AC: 87 AN: 15184

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4754

European-Finnish (FIN) AF: 0.000292 AC: 3 AN: 10262

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.000280 AC: 19 AN: 67804

Other (OTH) AF: 0.00678 AC: 14 AN: 2066

Alfa AF: 0.00316 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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;