rs147282516

Variant names:

• chr11-5253299-G-A
• rs147282516
• NM_000184.3:c.422C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5253299-G-A
• chr11-5253299-G-C
• chr11-5253299-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000184.3(HBG2):​c.422C>T​(p.Ala141Val) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HBG2 NM_000184.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72

Genes affected

HBG2 (HGNC:4832): (hemoglobin subunit gamma 2) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'- epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]

ENSG00000284931 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBG2	NM_000184.3	c.422C>T	p.Ala141Val	missense_variant	Exon 3 of 3	ENST00000336906.6	NP_000175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBG2	ENST00000336906.6	c.422C>T	p.Ala141Val	missense_variant	Exon 3 of 3	1	NM_000184.3	ENSP00000338082.4
ENSG00000284931	ENST00000642908.1	c.315+993C>T		intron_variant	Intron 2 of 2			ENSP00000495346.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	0.049
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	0.043	D
MutationAssessor	Uncertain	2.1	M;.
PROVEAN	Uncertain	-3.3	D;.
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.15	T;.
Polyphen		0.99	D;.
Vest4		0.33
MutPred		0.76		Loss of glycosylation at S140 (P = 0.0732);.;
MVP		0.94
ClinPred		0.86	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.39
gMVP		0.80

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

LitVar

Other links and lift over

dbSNP: rs147282516; hg19: chr11-5274529;