NM_016229.5:c.766C>G

Variant names:

• chr11-7665439-G-C
• NM_016229.5:c.766C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016229.5(CYB5R2):​c.766C>G​(p.Gln256Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: CYB5R2 NM_016229.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01

Genes affected

CYB5R2 (HGNC:24376): (cytochrome b5 reductase 2) The protein encoded by this gene belongs to the flavoprotein pyridine nucleotide cytochrome reductase family of proteins. Cytochrome b-type NAD(P)H oxidoreductases are implicated in many processes including cholesterol biosynthesis, fatty acid desaturation and elongation, and respiratory burst in neutrophils and macrophages. Cytochrome b5 reductases have soluble and membrane-bound forms that are the product of alternative splicing. In animal cells, the membrane-bound form binds to the endoplasmic reticulum, where it is a member of a fatty acid desaturation complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

PPFIBP2 (HGNC:9250): (PPFIA binding protein 2) This gene encodes a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. The encoded protein is a beta liprin and plays a role in axon guidance and neuronal synapse development by recruiting LAR protein-tyrosine phosphatases to the plasma membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22160995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYB5R2	NM_016229.5	c.766C>G	p.Gln256Glu	missense_variant	Exon 9 of 9	ENST00000299498.11	NP_057313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB5R2	ENST00000299498.11	c.766C>G	p.Gln256Glu	missense_variant	Exon 9 of 9	1	NM_016229.5	ENSP00000299498.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.766C>G (p.Q256E) alteration is located in exon 9 (coding exon 8) of the CYB5R2 gene. This alteration results from a C to G substitution at nucleotide position 766, causing the glutamine (Q) at amino acid position 256 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.057	T;T
Eigen	Benign	0.044
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Uncertain	0.029	D
MutationAssessor	Benign	0.96	L;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.37
Sift	Benign	0.13	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.0020	B;B
Vest4		0.22
MutPred		0.43		Loss of glycosylation at P253 (P = 0.0988);Loss of glycosylation at P253 (P = 0.0988);
MVP		0.95
MPC		0.0066
ClinPred		0.59	D
GERP RS		6.0
Varity_R		0.22
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr11-7686670;