rs1553213630

Variant names:

• chr1-152312492-GCTCACCTGGTAGAGG-CTGAGGA
• rs1553213630
• NM_002016.2:c.2379_2394delCCTCTACCAGGTGAGCinsTCCTCAG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_002016.2(FLG):​c.2379_2394delCCTCTACCAGGTGAGCinsTCCTCAG​(p.Leu794_Ser798delinsProGln) variant causes a missense, disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: FLG NM_002016.2 missense, disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.770
• Publications: 1 publications found

Genes affected

FLG (HGNC:3748): (filaggrin) The protein encoded by this gene is an intermediate filament-associated protein that aggregates keratin intermediate filaments in mammalian epidermis. It is initially synthesized as a polyprotein precursor, profilaggrin (consisting of multiple filaggrin units of 324 aa each), which is localized in keratohyalin granules, and is subsequently proteolytically processed into individual functional filaggrin molecules. Mutations in this gene are associated with ichthyosis vulgaris.[provided by RefSeq, Dec 2009]

CCDST (HGNC:55988): (cervical cancer associated DHX9 suppressive transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_002016.2.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002016.2. 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
	FLG	NM_002016.2	MANE Select	c.2379_2394delCCTCTACCAGGTGAGCinsTCCTCAG	p.Leu794_Ser798delinsProGln	missense disruptive_inframe_deletion	N/A	NP_002007.1	P20930
	CCDST	NR_186761.1		n.578-20091_578-20076delGCTCACCTGGTAGAGGinsCTGAGGA		intron	N/A
	CCDST	NR_186762.1		n.180-20091_180-20076delGCTCACCTGGTAGAGGinsCTGAGGA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLG	ENST00000368799.2	TSL:1 MANE Select	c.2379_2394delCCTCTACCAGGTGAGCinsTCCTCAG	p.Leu794_Ser798delinsProGln	missense disruptive_inframe_deletion	N/A	ENSP00000357789.1	P20930
	CCDST	ENST00000420707.5	TSL:5	n.463-2414_463-2399delGCTCACCTGGTAGAGGinsCTGAGGA		intron	N/A
	CCDST	ENST00000593011.5	TSL:4	n.377-2414_377-2399delGCTCACCTGGTAGAGGinsCTGAGGA		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Ichthyosis vulgaris;C1853965:Dermatitis, atopic, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77

Splicing

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

Other links and lift over

dbSNP: rs1553213630; hg19: chr1-152284968;