NM_002262.5:c.73T>G

Variant names:

• chr12-10309453-T-G
• rs10772256
• NM_002262.5:c.73T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002262.5(KLRD1):​c.73T>G​(p.Ser25Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 1,538,986 control chromosomes in the GnomAD database, including 752,439 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.94 (67394 hom., cov: 32)
  • Exomes 𝑓: 0.99 (685045 hom.)
• Consequence: KLRD1 NM_002262.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 28 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2583243E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002262.5. 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
	KLRD1	NM_002262.5	MANE Select	c.73T>G	p.Ser25Ala	missense	Exon 2 of 6	NP_002253.2
	KLRD1	NM_001351060.2		c.73T>G	p.Ser25Ala	missense	Exon 4 of 9	NP_001337989.1
	KLRD1	NM_001414224.1		c.73T>G	p.Ser25Ala	missense	Exon 2 of 7	NP_001401153.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRD1	ENST00000336164.9	TSL:1 MANE Select	c.73T>G	p.Ser25Ala	missense	Exon 2 of 6	ENSP00000338130.4
	KLRD1	ENST00000381908.7	TSL:1	c.73T>G	p.Ser25Ala	missense	Exon 3 of 7	ENSP00000371333.4
	KLRD1	ENST00000543777.5	TSL:1	c.73T>G	p.Ser25Ala	missense	Exon 2 of 5	ENSP00000443584.1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142344 AN: 152104 Hom.: 67366 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.951

GnomAD2 exomes AF: 0.983 AC: 247064 AN: 251362 AF XY: 0.988

Gnomad AFR exome AF: 0.767

Gnomad AMR exome AF: 0.989

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.992

GnomAD4 exome AF: 0.993 AC: 1377499 AN: 1386764 Hom.: 685045 Cov.: 24 AF XY: 0.994 AC XY: 690840 AN XY: 694772

African (AFR) AF: 0.772 AC: 24707 AN: 32024

American (AMR) AF: 0.987 AC: 44080 AN: 44642

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25666 AN: 25672

East Asian (EAS) AF: 1.00 AC: 39304 AN: 39304

South Asian (SAS) AF: 1.00 AC: 84665 AN: 84706

European-Finnish (FIN) AF: 1.00 AC: 53386 AN: 53386

Middle Eastern (MID) AF: 0.989 AC: 5567 AN: 5628

European-Non Finnish (NFE) AF: 1.00 AC: 1043192 AN: 1043614

Other (OTH) AF: 0.985 AC: 56932 AN: 57788

GnomAD4 genome AF: 0.936 AC: 142424 AN: 152222 Hom.: 67394 Cov.: 32 AF XY: 0.938 AC XY: 69828 AN XY: 74432

African (AFR) AF: 0.776 AC: 32193 AN: 41494

American (AMR) AF: 0.977 AC: 14945 AN: 15292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 0.999 AC: 4817 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67995 AN: 68030

Other (OTH) AF: 0.952 AC: 2008 AN: 2110

Alfa AF: 0.977 Hom.: 183837

Bravo AF: 0.926

TwinsUK AF: 0.999 AC: 3705

ALSPAC AF: 0.999 AC: 3852

ESP6500AA AF: 0.771 AC: 3395

ESP6500EA AF: 1.00 AC: 8596

ExAC AF: 0.979 AC: 118848

Asia WGS AF: 0.988 AC: 3438 AN: 3478

EpiCase AF: 0.999

EpiControl AF: 0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.10
DANN	Benign	0.18
DEOGEN2	Benign	0.067	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00033	N
LIST_S2	Benign	0.0055	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.7	N
PhyloP100		-0.11
PrimateAI	Benign	0.30	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.034
Sift	Benign	1.0	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.069
MPC		0.12
ClinPred		0.012	T
GERP RS		-3.8
Varity_R		0.036
gMVP		0.12
Mutation Taster		=99/1	polymorphism (auto)

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: rs10772256; hg19: chr12-10462052; COSMIC: COSV107399226; COSMIC: COSV107399226;