rs34956202

Variant names:

• chr16-172959-G-A
• rs34956202
• NM_000517.6:c.47G>A

Variant summary

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

The NM_000517.6(HBA2):​c.47G>A​(p.Gly16Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as other (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G16R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 2)
• Consequence: HBA2 NM_000517.6 missense
• Clinical Significance: other no assertion criteria provided O:3
• Conservation: PhyloP100: -3.11

Genes affected

HBA2 (HGNC:4824): (hemoglobin subunit alpha 2) The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5'- zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta - 3'. The alpha-2 (HBA2) and alpha-1 (HBA1) coding sequences are identical. These genes differ slightly over the 5' untranslated regions and the introns, but they differ significantly over the 3' untranslated regions. Two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin; alpha chains combine with delta chains to constitute HbA-2, which with HbF (fetal hemoglobin) makes up the remaining 3% of adult hemoglobin. Alpha thalassemias result from deletions of each of the alpha genes as well as deletions of both HBA2 and HBA1; some nondeletion alpha thalassemias have also been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBA2	NM_000517.6	c.47G>A	p.Gly16Asp	missense_variant	Exon 1 of 3	ENST00000251595.11	NP_000508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBA2	ENST00000251595.11	c.47G>A	p.Gly16Asp	missense_variant	Exon 1 of 3	1	NM_000517.6	ENSP00000251595.6
HBA2	ENST00000484216.1	c.14G>A	p.Gly5Asp	missense_variant	Exon 1 of 2	1		ENSP00000495899.1
HBA2	ENST00000482565.1	n.66G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
HBA2	ENST00000397806.1	c.-2+1G>A		splice_donor_variant, intron_variant	Intron 1 of 2	2		ENSP00000380908.1

Frequencies

GnomAD3 genomes Cov.: 2

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 2

ClinVar

Significance: other

Submissions summary: Other:3

Revision: no assertion criteria provided

Submissions by phenotype

HEMOGLOBIN I (INTERLAKEN) Other:1

Oct 13, 2016

OMIM

Significance: other

Review Status: no assertion criteria provided

Collection Method: literature only

- -

HEMOGLOBIN N (COSENZA) Other:1

Oct 13, 2016

OMIM

Significance: other

Review Status: no assertion criteria provided

Collection Method: literature only

- -

HEMOGLOBIN J (OXFORD) Other:1

Oct 13, 2016

OMIM

Significance: other

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	2.3
DANN	Benign	0.80
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.030	N
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.47	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.25	N
REVEL	Uncertain	0.52
Sift	Benign	0.26	T
Sift4G	Benign	0.50	T
Vest4		0.48
MutPred		0.83		Loss of MoRF binding (P = 0.0422);
MVP		0.98
MPC		1.6
ClinPred		0.10	T
GERP RS		-2.4
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs34956202; hg19: chr16-222958;