1-196949604-A-G

Position:

• chr1-196949604-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005666.4(CFHR2):​c.208A>G​(p.Ile70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFHR2 NM_005666.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30302644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR2	NM_005666.4	c.208A>G	p.Ile70Val	missense_variant	2/5	ENST00000367415.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR2	ENST00000367415.8	c.208A>G	p.Ile70Val	missense_variant	2/5	1	NM_005666.4	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Jan 30, 2023

BP4, PM2_supporting -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0062	.;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.9	.;M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.83	N;N;.
REVEL	Benign	0.24
Sift	Benign	0.23	T;T;.
Sift4G	Benign	0.12	.;T;T
Polyphen		1.0	.;D;.
Vest4		0.35, 0.36
MutPred		0.56		.;Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.59
MPC		0.038
ClinPred		0.72	D
GERP RS		3.1
Varity_R		0.067
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-196918734;