rs2844577

chr6-31366645-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000414224.1(DHFRP2):n.254A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,389,596 control chromosomes in the GnomAD database, including 10,985 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.078 (630 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10355 hom.)
• Consequence: DHFRP2 ENST00000414224.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831

Genes affected

DHFRP2 (HGNC:2863): (dihydrofolate reductase pseudogene 2)

(HGNC:):

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B 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. 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, exon 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. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHFRP2	ENST00000414224.1	n.254A>G		non_coding_transcript_exon_variant	1/1
	ENST00000696690.1	n.710A>G		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11905 AN: 152122 Hom.: 630 Cov.: 32

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0388

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.00480

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.0860

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0617

GnomAD4 exome AF: 0.117 AC: 144982 AN: 1237356 Hom.: 10355 Cov.: 24 AF XY: 0.116 AC XY: 72745 AN XY: 626398

Gnomad4 AFR exome AF: 0.0361

Gnomad4 AMR exome AF: 0.0300

Gnomad4 ASJ exome AF: 0.0457

Gnomad4 EAS exome AF: 0.00145

Gnomad4 SAS exome AF: 0.0826

Gnomad4 FIN exome AF: 0.0877

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0782 AC: 11909 AN: 152240 Hom.: 630 Cov.: 32 AF XY: 0.0739 AC XY: 5498 AN XY: 74428

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.0387

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.00462

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.0860

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.113 Hom.: 482

Bravo AF: 0.0720

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	12
Dann	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2844577; hg19: chr6-31334422;