6-32838012-G-C

Variant names:

• chr6-32838012-G-C
• rs2229526
• NM_001290043.2:c.222C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000374897.4(TAP2):​c.222C>G​(p.Pro74Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P74P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TAP2 ENST00000374897.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 2 publications found

Genes affected

TAP2 (HGNC:44): (transporter 2, ATP binding cassette subfamily B member) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. This gene is located 7 kb telomeric to gene family member ABCB2. The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to transport peptides from the cytoplasm to the endoplasmic reticulum. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Alternative splicing of this gene produces products which differ in peptide selectivity and level of restoration of surface expression of MHC class I molecules. [provided by RefSeq, Feb 2014]

TAP2 Gene-Disease associations (from GenCC):

• MHC class I deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000250264 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.809 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374897.4. 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
	TAP2	NM_001290043.2	MANE Select	c.222C>G	p.Pro74Pro	synonymous	Exon 2 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.222C>G	p.Pro74Pro	synonymous	Exon 2 of 12	NP_061313.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.222C>G	p.Pro74Pro	synonymous	Exon 2 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.222C>G	p.Pro74Pro	synonymous	Exon 2 of 15	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.222C>G	p.Pro74Pro	synonymous	Exon 2 of 13	ENSP00000513734.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151886 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000242

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000813 AC: 2 AN: 245934 AF XY: 0.00000745

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000907

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460530 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 726562

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111884

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151886 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 74160

African (AFR) AF: 0.0000242 AC: 1 AN: 41306

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.42
DANN	Benign	0.59
PhyloP100		-0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2229526; hg19: chr6-32805789;