6-32816899-C-G

Variant names:

• chr6-32816899-C-G
• rs2071554
• NM_002120.4:c.53G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002120.4(HLA-DOB):​c.53G>C​(p.Arg18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HLA-DOB NM_002120.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538
• Publications: 0 publications found

Genes affected

HLA-DOB (HGNC:4937): (major histocompatibility complex, class II, DO beta) HLA-DOB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DOA) and a beta chain (DOB), both anchored in the membrane. It is located in intracellular vesicles. DO suppresses peptide loading of MHC class II molecules by inhibiting HLA-DM. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

ENSG00000250264 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24104267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002120.4. 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
	HLA-DOB	NM_002120.4	MANE Select	c.53G>C	p.Arg18Pro	missense	Exon 1 of 6	NP_002111.1	P13765

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DOB	ENST00000438763.7	TSL:6 MANE Select	c.53G>C	p.Arg18Pro	missense	Exon 1 of 6	ENSP00000390020.2	P13765
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1986G>C	p.Pro662Pro	synonymous	Exon 12 of 15	ENSP00000391806.2	E7ENX8
	HLA-DOB	ENST00000648009.1		c.53G>C	p.Arg18Pro	missense	Exon 2 of 7	ENSP00000496848.1	P13765

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.049	N
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.54
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.21
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.045	D
Polyphen		0.93	P
Vest4		0.25
MutPred		0.45		Loss of methylation at R18 (P = 0.0222)
MVP		0.32
MPC		0.51
ClinPred		0.58	D
GERP RS		3.5
PromoterAI		-0.26	Neutral
Varity_R		0.18
gMVP		0.70
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2071554; hg19: chr6-32784676;