22-36922275-G-C

Position:

• chr22-36922275-G-C

Variant summary

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

The NM_000395.3(CSF2RB):​c.68G>C​(p.Gly23Ala) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSF2RB NM_000395.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.562

Genes affected

CSF2RB (HGNC:2436): (colony stimulating factor 2 receptor subunit beta) The protein encoded by this gene is the common beta chain of the high affinity receptor for IL-3, IL-5 and CSF. Defects in this gene have been reported to be associated with protein alveolar proteinosis (PAP). [provided by RefSeq, Jul 2008]

LOC105373023 (HGNC:):

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=0.17641875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.68G>C	p.Gly23Ala	missense_variant	2/14	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.68G>C	p.Gly23Ala	missense_variant	2/14	5	NM_000395.3	ENSP00000384053.3
CSF2RB	ENST00000406230.5	c.68G>C	p.Gly23Ala	missense_variant	1/13	1		ENSP00000385271.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Labcorp Genetics (formerly Invitae), Labcorp

Sep 05, 2023

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 23 of the CSF2RB protein (p.Gly23Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CSF2RB-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CSF2RB protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.3
DANN	Benign	0.95
DEOGEN2	Uncertain	0.45	T;T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.4	L;.;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.29
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.92	P;.;P
Vest4		0.22
MutPred		0.41		Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);
MVP		0.80
MPC		0.32
ClinPred		0.19	T
GERP RS		-2.2
Varity_R		0.041
gMVP		0.40

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: chr22-37318317;