rs61736918

Variant names:

• chr6-32838230-G-A
• rs61736918
• NM_001290043.2:c.4C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32838230-G-A
• chr6-32838230-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001290043.2(TAP2):​c.4C>T​(p.Arg2Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000968 in 1,563,374 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0042 (5 hom., cov: 27)
  • Exomes 𝑓: 0.00063 (3 hom.)
• Consequence: TAP2 NM_001290043.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.180
• Publications: 4 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008757621).
• BP6: Variant 6-32838230-G-A is Benign according to our data. Variant chr6-32838230-G-A is described in ClinVar as Benign. ClinVar VariationId is 466373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0042 (623/148446) while in subpopulation AFR AF = 0.0124 (496/40046). AF 95% confidence interval is 0.0115. There are 5 homozygotes in GnomAd4. There are 316 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290043.2. 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.4C>T	p.Arg2Trp	missense	Exon 2 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.4C>T	p.Arg2Trp	missense	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.4C>T	p.Arg2Trp	missense	Exon 2 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.4C>T	p.Arg2Trp	missense	Exon 2 of 15	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.4C>T	p.Arg2Trp	missense	Exon 2 of 13	ENSP00000513734.1

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 624 AN: 148328 Hom.: 5 Cov.: 27

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00638

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000328

Gnomad OTH AF: 0.00503

GnomAD2 exomes AF: 0.00194 AC: 400 AN: 206168 AF XY: 0.00157

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.00580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000382

Gnomad OTH exome AF: 0.000809

GnomAD4 exome AF: 0.000630 AC: 891 AN: 1414928 Hom.: 3 Cov.: 35 AF XY: 0.000543 AC XY: 380 AN XY: 700420

African (AFR) AF: 0.0103 AC: 328 AN: 31830

American (AMR) AF: 0.00586 AC: 222 AN: 37908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22810

East Asian (EAS) AF: 0.00 AC: 0 AN: 39338

South Asian (SAS) AF: 0.00 AC: 0 AN: 79536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49572

Middle Eastern (MID) AF: 0.00119 AC: 5 AN: 4198

European-Non Finnish (NFE) AF: 0.000221 AC: 241 AN: 1091486

Other (OTH) AF: 0.00163 AC: 95 AN: 58250

GnomAD4 genome AF: 0.00420 AC: 623 AN: 148446 Hom.: 5 Cov.: 27 AF XY: 0.00437 AC XY: 316 AN XY: 72264

African (AFR) AF: 0.0124 AC: 496 AN: 40046

American (AMR) AF: 0.00637 AC: 94 AN: 14764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10200

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000328 AC: 22 AN: 67148

Other (OTH) AF: 0.00497 AC: 10 AN: 2012

Alfa AF: 0.00164 Hom.: 5

Bravo AF: 0.00567

ESP6500AA AF: 0.0126 AC: 38

ESP6500EA AF: 0.000738 AC: 4

ExAC AF: 0.00164 AC: 194

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class I deficiency Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.089	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.86	D
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.18
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.035	D
Polyphen		0.0020	B
Vest4		0.12
MVP		0.39
MPC		0.47
ClinPred		0.035	T
GERP RS		-5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.29
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs61736918; hg19: chr6-32806007; COSMIC: COSV66487501; COSMIC: COSV66487501;