rs1051456
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001080770.2(KIR2DL4):c.625C>A(p.Pro209Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. P209L) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 29)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KIR2DL4
NM_001080770.2 missense
NM_001080770.2 missense
Scores
2
2
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.400
Publications
17 publications found
Genes affected
KIR2DL4 (HGNC:6332): (killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 4) Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. This gene is one of the "framework" loci that is present on all haplotypes. Alternate alleles of this gene are represented on multiple alternate reference loci (ALT_REF_LOCs). Alternative splicing results in multiple transcript variants, some of which may not be annotated on the primary reference assembly. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification was made for transcript
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=0.1321306).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001080770.2. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KIR2DL4 | TSL:1 MANE Select | c.625C>A | p.Pro209Thr | missense | Exon 4 of 7 | ENSP00000339634.5 | Q99706-3 | ||
| KIR2DL4 | TSL:1 | c.625C>A | p.Pro209Thr | missense | Exon 4 of 6 | ENSP00000350088.4 | Q99706-4 | ||
| KIR2DL4 | TSL:1 | c.625C>A | p.Pro209Thr | missense | Exon 4 of 8 | ENSP00000351988.4 | A0A0B4J1S6 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 149666Hom.: 0 Cov.: 29
GnomAD3 genomes
AF:
AC:
0
AN:
149666
Hom.:
Cov.:
29
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457472Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1AN XY: 725076 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1457472
Hom.:
Cov.:
38
AF XY:
AC XY:
1
AN XY:
725076
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33218
American (AMR)
AF:
AC:
0
AN:
44640
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25976
East Asian (EAS)
AF:
AC:
0
AN:
39662
South Asian (SAS)
AF:
AC:
1
AN:
85754
European-Finnish (FIN)
AF:
AC:
0
AN:
52874
Middle Eastern (MID)
AF:
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1109352
Other (OTH)
AF:
AC:
0
AN:
60252
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00 AC: 0AN: 149666Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 72910
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
149666
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
72910
African (AFR)
AF:
AC:
0
AN:
40056
American (AMR)
AF:
AC:
0
AN:
15058
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3418
East Asian (EAS)
AF:
AC:
0
AN:
5104
South Asian (SAS)
AF:
AC:
0
AN:
4652
European-Finnish (FIN)
AF:
AC:
0
AN:
10426
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67674
Other (OTH)
AF:
AC:
0
AN:
2052
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H
PhyloP100
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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