Variant 19-54741976-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015868.3(KIR2DL3):c.71-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 112,370 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.12 ( 2 hom., cov: 28)

Exomes 𝑓: 0.17 ( 44 hom. )

Failed GnomAD Quality Control

Consequence

KIR2DL3
NM_015868.3 splice_region, intron

Scores

Splicing: ADA: 0.00003298

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -1.19

Variant links:

Genes affected

KIR2DL3 (HGNC:6331): (killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 3) 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. [provided by RefSeq, Jul 2008]

KIR2DL3 links:

ENSG00000215765 (HGNC:):

ENSG00000215765 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIR2DL3	NM_015868.3 link	c.71-4C>T		splice_region_variant, intron_variant		ENST00000342376.4	NP_056952.2	P43628-1E3NZD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIR2DL3	ENST00000342376.4 link	c.71-4C>T		splice_region_variant, intron_variant		1	NM_015868.3	ENSP00000342215.3		P43628-1
ENSG00000215765	ENST00000400864.3 link	n.35+17446C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

13673

AN:

112272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.0865

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.0486

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.0958

Gnomad MID

AF:

0.183

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.126

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.169

AC:

189717

AN:

1125568

Hom.:

Cov.:

AF XY:

0.171

AC XY:

95199

AN XY:

557030

show subpopulations

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.0461

Gnomad4 SAS exome

AF:

0.249

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.122

AC:

13688

AN:

112370

Hom.:

Cov.:

AF XY:

0.122

AC XY:

6706

AN XY:

54944

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.141

Gnomad4 ASJ

AF:

0.178

Gnomad4 EAS

AF:

0.0487

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.0958

Gnomad4 NFE

AF:

0.131

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.118

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Malignant tumor of prostate

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.58

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over