rs10772256

Positions:

• chr12-10309453-T-A
• chr12-10309453-T-C
• chr12-10309453-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002262.5(KLRD1):​c.73T>A​(p.Ser25Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. S25A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLRD1 NM_002262.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

Genes affected

KLRD1 (HGNC:6378): (killer cell lectin like receptor D1) Natural killer (NK) cells are a distinct lineage of lymphocytes that mediate cytotoxic activity and secrete cytokines upon immune stimulation. Several genes of the C-type lectin superfamily, including members of the NKG2 family, are expressed by NK cells and may be involved in the regulation of NK cell function. KLRD1 (CD94) is an antigen preferentially expressed on NK cells and is classified as a type II membrane protein because it has an external C terminus. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

KLRD1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061225712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRD1	NM_002262.5	c.73T>A	p.Ser25Thr	missense_variant	2/6	ENST00000336164.9	NP_002253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRD1	ENST00000336164.9	c.73T>A	p.Ser25Thr	missense_variant	2/6	1	NM_002262.5	ENSP00000338130.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1386910 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 694834

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.0
DANN	Benign	0.71
DEOGEN2	Benign	0.085	T;T;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.025	.;T;.;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.061	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.38	N;N;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.36	N;N;N;N
REVEL	Benign	0.015
Sift	Benign	0.048	D;D;D;T
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.095
MutPred		0.50		Gain of catalytic residue at S22 (P = 0);Gain of catalytic residue at S22 (P = 0);Gain of catalytic residue at S22 (P = 0);Gain of catalytic residue at S22 (P = 0);
MVP		0.16
MPC		0.13
ClinPred		0.057	T
GERP RS		-3.8
Varity_R		0.045
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs10772256; hg19: chr12-10462052;