rs2231004

Variant names:

• chr6-29942985-A-C
• rs2231004
• NM_002116.8:c.302A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-29942985-A-C
• chr6-29942985-A-G
• chr6-29942985-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002116.8(HLA-A):​c.302A>C​(p.Asp101Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D101N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 5)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-A NM_002116.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 0 publications found

Genes affected

HLA-A (HGNC:4931): (major histocompatibility complex, class I, A) HLA-A belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen so that they can be recognized by cytotoxic T cells. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. More than 6000 HLA-A alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]

ENSG00000227766 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.083672315).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002116.8. 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-A	NM_002116.8	MANE Select	c.302A>C	p.Asp101Ala	missense	Exon 2 of 8	NP_002107.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-A	ENST00000376809.10	TSL:6 MANE Select	c.302A>C	p.Asp101Ala	missense	Exon 2 of 8	ENSP00000366005.5	P04439-1
	HLA-A	ENST00000952344.1		c.302A>C	p.Asp101Ala	missense	Exon 2 of 8	ENSP00000622403.1
	HLA-A	ENST00000706894.1		c.302A>C	p.Asp101Ala	missense	Exon 3 of 8	ENSP00000516610.1	A0A9L9PYF9

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 52346 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1017292 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 503660

African (AFR) AF: 0.00 AC: 0 AN: 22820

American (AMR) AF: 0.00 AC: 0 AN: 24894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15888

East Asian (EAS) AF: 0.00 AC: 0 AN: 13930

South Asian (SAS) AF: 0.00 AC: 0 AN: 63146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 796376

Other (OTH) AF: 0.00 AC: 0 AN: 40112

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 52346 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 25608

African (AFR) AF: 0.00 AC: 0 AN: 10966

American (AMR) AF: 0.00 AC: 0 AN: 3640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 984

East Asian (EAS) AF: 0.00 AC: 0 AN: 1764

South Asian (SAS) AF: 0.00 AC: 0 AN: 1562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 84

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 27184

Other (OTH) AF: 0.00 AC: 0 AN: 642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.8
DANN	Benign	0.30
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.0054	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.95	T
PhyloP100		-1.5
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.12
Sift	Benign	0.038	D
Sift4G	Uncertain	0.060	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.21		Gain of sheet (P = 0.0101)
MVP		0.15
MPC		0.11
ClinPred		0.094	T
GERP RS		-3.8
PromoterAI		0.037	Neutral
Varity_R		0.31
gMVP		0.20
Mutation Taster		=99/1	polymorphism

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: rs2231004; hg19: chr6-29910762;