1-196949602-GC-TG

Variant names:

• chr1-196949602-GC-TG
• NM_005666.4:c.206_207delGCinsTG
• CFHR2 p.Arg69Leu

Variant summary

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

The NM_005666.4(CFHR2):​c.206_207delGCinsTG​(p.Arg69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CFHR2 NM_005666.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.22
• Publications: 0 publications found

Genes affected

CFHR2 (HGNC:4890): (complement factor H related 2) This gene belongs to a family of complement factor H-related genes (CFHR), which are clustered together with complement factor H gene on chromosome 1, and are involved in regulation of complement. Mutations in CFHR genes have been associated with dense deposit disease and atypical haemolytic-uraemic syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005666.4. 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
	CFHR2	NM_005666.4	MANE Select	c.206_207delGCinsTG	p.Arg69Leu	missense	N/A	NP_005657.1	P36980-1
	CFHR2	NM_001410924.1		c.59-1250_59-1249delGCinsTG		intron	N/A	NP_001397853.1	A0A3B3IRW0
	CFHR2	NM_001312672.1		c.58+5664_58+5665delGCinsTG		intron	N/A	NP_001299601.1	A0A3B3IS28

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR2	ENST00000367415.8	TSL:1 MANE Select	c.206_207delGCinsTG	p.Arg69Leu	missense	N/A	ENSP00000356385.4	P36980-1
	CFHR2	ENST00000367421.5	TSL:1	c.461_462delGCinsTG	p.Arg154Leu	missense	N/A	ENSP00000356391.4	A0A3B3IQ51
	CFHR2	ENST00000473386.1	TSL:1	c.58+5664_58+5665delGCinsTG		intron	N/A	ENSP00000497089.1	A0A3B3IS28

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-196918732;