NM_000517.6:c.*107A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000517.6(HBA2):c.*107A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 148,818 control chromosomes in the GnomAD database, including 73,606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 73606 hom., cov: 32)

Exomes 𝑓: 0.99 ( 634691 hom. )

Failed GnomAD Quality Control

Consequence

HBA2
NM_000517.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.12

Publications

9 publications found

Variant links:

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]

HBA2 Gene-Disease associations (from GenCC):

alpha thalassemia spectrum
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
erythrocytosis, familial, 7
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
hemoglobin M disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Hb Bart's hydrops fetalis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hemoglobin H disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Heinz body anemia
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
methemoglobinemia, alpha type
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

HBA2 links:

ENSG00000294455 (HGNC:):

ENSG00000294455 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-173707-A-G is Benign according to our data. Variant chr16-173707-A-G is described in ClinVar as Benign. ClinVar VariationId is 439108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000517.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBA2	NM_000517.6	MANE Select	c.*107A>G		3_prime_UTR	Exon 3 of 3	NP_000508.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HBA2	ENST00000251595.11	TSL:1 MANE Select	c.*107A>G	3_prime_UTR	Exon 3 of 3	ENSP00000251595.6
ENSG00000294455	ENST00000723699.1		n.4T>C	non_coding_transcript_exon	Exon 1 of 2
ENSG00000294455	ENST00000723700.1		n.4T>C	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.994

AC:

147874

AN:

148696

Hom.:

73542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.993

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

0.992

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.992

Gnomad OTH

AF:

0.995

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.992

AC:

1279110

AN:

1288992

Hom.:

634691

Cov.:

AF XY:

0.993

AC XY:

639893

AN XY:

644634

show subpopulations

African (AFR)

AF:

0.999

AC:

25630

AN:

25656

American (AMR)

AF:

0.996

AC:

38282

AN:

38446

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

24446

AN:

24450

East Asian (EAS)

AF:

1.00

AC:

36587

AN:

36588

South Asian (SAS)

AF:

1.00

AC:

77341

AN:

77352

European-Finnish (FIN)

AF:

0.992

AC:

49505

AN:

49894

Middle Eastern (MID)

AF:

1.00

AC:

5326

AN:

5328

European-Non Finnish (NFE)

AF:

0.991

AC:

968409

AN:

977344

Other (OTH)

AF:

0.994

AC:

53584

AN:

53934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

529

1058

1587

2116

2645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18248

36496

54744

72992

91240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.994

AC:

147999

AN:

148818

Hom.:

73606

Cov.:

AF XY:

0.995

AC XY:

72346

AN XY:

72698

show subpopulations

African (AFR)

AF:

0.998

AC:

38483

AN:

38542

American (AMR)

AF:

0.993

AC:

15045

AN:

15144

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3465

AN:

3466

East Asian (EAS)

AF:

1.00

AC:

5164

AN:

5164

South Asian (SAS)

AF:

1.00

AC:

4616

AN:

4616

European-Finnish (FIN)

AF:

0.992

AC:

10535

AN:

10616

Middle Eastern (MID)

AF:

1.00

AC:

292

AN:

292

European-Non Finnish (NFE)

AF:

0.992

AC:

67412

AN:

67980

Other (OTH)

AF:

0.995

AC:

2075

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.994

Hom.:

9510

Bravo

AF:

0.994

Asia WGS

AF:

0.999

AC:

3191

AN:

3194

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

alpha Thalassemia (4)

not provided (2)

not specified (2)

Erythrocytosis, familial, 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.92

(source)

DANN

Benign

0.43

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over