rs2070972

Positions:

• chr11-5253487-A-C
• chr11-5253487-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000184.3(HBG2):​c.316-82T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,256,676 control chromosomes in the GnomAD database, including 149,289 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (15514 hom., cov: 31)
  • Exomes 𝑓: 0.48 (133775 hom.)
• Consequence: HBG2 NM_000184.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBG2	NM_000184.3	c.316-82T>G		intron_variant		ENST00000336906.6	NP_000175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBG2	ENST00000336906.6	c.316-82T>G		intron_variant		1	NM_000184.3	ENSP00000338082.4
ENSG00000284931	ENST00000642908.1	c.315+805T>G		intron_variant				ENSP00000495346.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 68065 AN: 141676 Hom.: 15501 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.610

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.484 AC: 540133 AN: 1114896 Hom.: 133775 AF XY: 0.487 AC XY: 275726 AN XY: 566448

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.622

Gnomad4 EAS exome AF: 0.732

Gnomad4 SAS exome AF: 0.546

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.505

GnomAD4 genome AF: 0.480 AC: 68117 AN: 141780 Hom.: 15514 Cov.: 31 AF XY: 0.485 AC XY: 33731 AN XY: 69550

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.523

Alfa AF: 0.453 Hom.: 1602

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.44

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: rs2070972; hg19: chr11-5274717;