rs869025338

Positions:

• chr10-13657442-C-CCCTGGGACTCCAG

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_018027.5(FRMD4A):​c.2134_2146dupCTGGAGTCCCAGG​(p.Gly716fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FRMD4A NM_018027.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.95

Genes affected

FRMD4A (HGNC:25491): (FERM domain containing 4A) This gene encodes a FERM domain-containing protein that regulates epithelial cell polarity. It connects ADP ribosylation factor 6 (ARF6) with the Par protein complex, which regulates the remodeling of adherens junctions and linear actin cable formation during epithelial cell polarization. Polymorphisms in this gene are associated with Alzheimer's disease, and also with nicotine dependence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

PRPF18 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-13657442-C-CCCTGGGACTCCAG is Pathogenic according to our data. Variant chr10-13657442-C-CCCTGGGACTCCAG is described in ClinVar as [Pathogenic]. Clinvar id is 222035.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.2134_2146dupCTGGAGTCCCAGG	p.Gly716fs	frameshift_variant	22/25	ENST00000357447.7	NP_060497.3
FRMD4A	NM_001318337.2	c.2233_2245dupCTGGAGTCCCAGG	p.Gly749fs	frameshift_variant	21/24		NP_001305266.1
FRMD4A	NM_001318336.2	c.2182_2194dupCTGGAGTCCCAGG	p.Gly732fs	frameshift_variant	21/24		NP_001305265.1
FRMD4A	NM_001318338.2	c.1207_1219dupCTGGAGTCCCAGG	p.Gly407fs	frameshift_variant	11/14		NP_001305267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.2134_2146dupCTGGAGTCCCAGG	p.Gly716fs	frameshift_variant	22/25	1	NM_018027.5	ENSP00000350032.2
FRMD4A	ENST00000495956.3	c.2134_2146dupCTGGAGTCCCAGG	p.Gly716fs	frameshift_variant	22/24	2		ENSP00000488764.2
PRPF18	ENST00000593351.2	n.47+9213_47+9225dupCCTGGGACTCCAG		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 17, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs869025338; hg19: chr10-13699442;