rs34907654

chr11-5254680-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4 BP6_Moderate

The NM_000184.3(HBG2):c.49G>C(p.Gly17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 23)
• Consequence: HBG2 NM_000184.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.0250

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3982432).
• BP6: Variant 11-5254680-C-G is Benign according to our data. Variant chr11-5254680-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 14973.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBG2	NM_000184.3	c.49G>C	p.Gly17Arg	missense_variant	1/3	ENST00000336906.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBG2	ENST00000336906.6	c.49G>C	p.Gly17Arg	missense_variant	1/3	1	NM_000184.3	P1
HBG2	ENST00000444587.1	c.49G>C	p.Gly17Arg	missense_variant	1/3	2
HBG2	ENST00000380252.6	c.-73-166G>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 9

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Feb 14, 2022

- -

HEMOGLOBIN F (MELBOURNE) Other:1

other, no assertion criteria provided

literature only

OMIM

Aug 05, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
Cadd	Benign	15
Dann	Uncertain	0.98
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.77	T;T;T;.
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-0.28	T
MutationTaster	Benign	1.0	D;N;N
Polyphen		0.0010	.;.;B;.
Vest4		0.17, 0.15
MutPred		0.69		Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);
MVP		0.75
ClinPred		0.15	T
GERP RS		-0.55
Varity_R		0.59
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34907654; hg19: chr11-5275910;