Variant 11-5254429-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_000184.3(HBG2):c.178A>C(p.Lys60Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K60E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

HBG2
NM_000184.3 missense

Scores

Clinical Significance

other no assertion criteria provided O:1

Conservation

PhyloP100: 2.75

Variant links:

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]

HBG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2

High AC in GnomAdExome4 at 11 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBG2	NM_000184.3 linkuse as main transcript	c.178A>C	p.Lys60Gln	missense_variant	2/3	ENST00000336906.6	NP_000175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HBG2	ENST00000336906.6 linkuse as main transcript	c.178A>C	p.Lys60Gln	missense_variant	2/3	1	NM_000184.3	ENSP00000338082	P1
HBG2	ENST00000380252.6 linkuse as main transcript	c.13A>C	p.Lys5Gln	missense_variant	2/3	3		ENSP00000369602
HBG2	ENST00000444587.1 linkuse as main transcript	c.*47A>C		3_prime_UTR_variant	2/3	2		ENSP00000488218

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251458

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HEMOGLOBIN F (SACROMONTE)

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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.070

.;.;T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.53

D;D;D;D

MetaSVM

Uncertain

-0.091

MutationAssessor

Benign

1.8

.;.;L;.

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-2.2

.;.;N;.

REVEL

Uncertain

0.61

Sift

Uncertain

0.015

.;.;D;.

Sift4G

Benign

0.26

.;.;T;.

Polyphen

0.0060

.;.;B;.

Vest4

0.64

MutPred

0.66

Loss of methylation at K60 (P = 0.0101);Loss of methylation at K60 (P = 0.0101);Loss of methylation at K60 (P = 0.0101);.;

MVP

0.88

ClinPred

0.19

GERP RS

2.7

Varity_R

0.42

gMVP

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over