chr11-5234372-A-T

Variant names:

• chr11-5234372-A-T
• rs34093840
• NM_000519.4:c.62T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000519.4(HBD):​c.62T>A​(p.Val21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HBD NM_000519.4 missense
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 1.17
• Publications: 1 publications found

Genes affected

HBD (HGNC:4829): (hemoglobin subunit delta) The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute HbA-2, which with HbF comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon--Ggamma--Agamma--delta--beta-3'. Mutations in the delta-globin gene are associated with beta-thalassemia. [provided by RefSeq, Jul 2008]

HBD Gene-Disease associations (from GenCC):

• delta-beta-thalassemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000298932 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000519.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBD	NM_000519.4	MANE Select	c.62T>A	p.Val21Glu	missense	Exon 1 of 3	NP_000510.1	P02042

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBD	ENST00000650601.1	MANE Select	c.62T>A	p.Val21Glu	missense	Exon 1 of 3	ENSP00000497529.1	P02042
	HBD	ENST00000643122.1		c.62T>A	p.Val21Glu	missense	Exon 2 of 4	ENSP00000494708.1	P02042
	HBD	ENST00000292901.7	TSL:3	c.62T>A	p.Val21Glu	missense	Exon 1 of 3	ENSP00000292901.3	E9PFT6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: other

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	HEMOGLOBIN A(2) ROOSEVELT (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.2
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.012	D
Sift4G	Benign	0.065	T
Polyphen		0.0090	B
Vest4		0.36
MutPred		0.61		Gain of disorder (P = 0.013)
MVP		0.84
MPC		0.013
ClinPred		0.071	T
GERP RS		-0.87
PromoterAI		-0.0089	Neutral
Varity_R		0.51
gMVP		0.81
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs34093840; hg19: chr11-5255602;