rs12692566

Variant names:

• chr2-159819916-C-A
• rs12692566
• NM_002349.4:c.3963G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-159819916-C-A
• chr2-159819916-C-G
• chr2-159819916-C-T

Variant summary

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

The NM_002349.4(LY75):​c.3963G>T​(p.Lys1321Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,594,716 control chromosomes in the GnomAD database, including 548,338 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (54310 hom., cov: 32)
  • Exomes 𝑓: 0.83 (494028 hom.)
• Consequence: LY75 NM_002349.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517
• Publications: 42 publications found

Genes affected

LY75 (HGNC:6729): (lymphocyte antigen 75) Predicted to enable signaling receptor activity. Predicted to be involved in immune response and inflammatory response. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LY75-CD302 (HGNC:38828): (LY75-CD302 readthrough) This locus represents naturally occurring read-through transcription between the neighboring lymphocyte antigen 75 (LY75) and CD302 molecule (CD302) genes. Alternative splicing results in multiple transcript variants encoding fusion products that share sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=8.3575503E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY75	NM_002349.4	c.3963G>T	p.Lys1321Asn	missense_variant	Exon 29 of 35	ENST00000263636.5	NP_002340.2
LY75-CD302	NM_001198759.1	c.3963G>T	p.Lys1321Asn	missense_variant	Exon 29 of 39		NP_001185688.1
LY75-CD302	NM_001198760.1	c.3963G>T	p.Lys1321Asn	missense_variant	Exon 29 of 38		NP_001185689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY75	ENST00000263636.5	c.3963G>T	p.Lys1321Asn	missense_variant	Exon 29 of 35	1	NM_002349.4	ENSP00000263636.4
LY75-CD302	ENST00000504764.5	c.3963G>T	p.Lys1321Asn	missense_variant	Exon 29 of 39	2		ENSP00000423463.1
LY75-CD302	ENST00000505052.1	c.3963G>T	p.Lys1321Asn	missense_variant	Exon 29 of 38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128269 AN: 152050 Hom.: 54252 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.845

GnomAD2 exomes AF: 0.826 AC: 193416 AN: 234094 AF XY: 0.819

Gnomad AFR exome AF: 0.885

Gnomad AMR exome AF: 0.878

Gnomad ASJ exome AF: 0.830

Gnomad EAS exome AF: 0.898

Gnomad FIN exome AF: 0.793

Gnomad NFE exome AF: 0.821

Gnomad OTH exome AF: 0.827

GnomAD4 exome AF: 0.827 AC: 1192413 AN: 1442550 Hom.: 494028 Cov.: 44 AF XY: 0.823 AC XY: 590132 AN XY: 717100

African (AFR) AF: 0.893 AC: 28719 AN: 32168

American (AMR) AF: 0.879 AC: 34803 AN: 39578

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 20666 AN: 25024

East Asian (EAS) AF: 0.911 AC: 35995 AN: 39500

South Asian (SAS) AF: 0.726 AC: 59557 AN: 82030

European-Finnish (FIN) AF: 0.795 AC: 42177 AN: 53054

Middle Eastern (MID) AF: 0.774 AC: 4377 AN: 5654

European-Non Finnish (NFE) AF: 0.829 AC: 917028 AN: 1106126

Other (OTH) AF: 0.826 AC: 49091 AN: 59416

GnomAD4 genome AF: 0.844 AC: 128392 AN: 152166 Hom.: 54310 Cov.: 32 AF XY: 0.840 AC XY: 62503 AN XY: 74366

African (AFR) AF: 0.887 AC: 36847 AN: 41530

American (AMR) AF: 0.881 AC: 13471 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2873 AN: 3470

East Asian (EAS) AF: 0.897 AC: 4649 AN: 5182

South Asian (SAS) AF: 0.723 AC: 3490 AN: 4828

European-Finnish (FIN) AF: 0.796 AC: 8387 AN: 10532

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.823 AC: 55958 AN: 68008

Other (OTH) AF: 0.847 AC: 1791 AN: 2114

Alfa AF: 0.830 Hom.: 164545

Bravo AF: 0.857

TwinsUK AF: 0.843 AC: 3125

ALSPAC AF: 0.823 AC: 3172

ESP6500AA AF: 0.890 AC: 3915

ESP6500EA AF: 0.828 AC: 7118

ExAC AF: 0.824 AC: 99962

Asia WGS AF: 0.842 AC: 2926 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.40
DEOGEN2	Benign	0.021	.;.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.17	T;T;T
MetaRNN	Benign	8.4e-7	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.6	.;.;N
PhyloP100		0.52
PROVEAN	Benign	1.9	N;N;N
REVEL	Benign	0.071
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.053
MutPred		0.56		Loss of ubiquitination at K1321 (P = 0.0155);Loss of ubiquitination at K1321 (P = 0.0155);Loss of ubiquitination at K1321 (P = 0.0155);
MPC		0.055
ClinPred		0.0061	T
GERP RS		4.5
Varity_R		0.18
gMVP		0.33
Mutation Taster		=97/3	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: rs12692566; hg19: chr2-160676427; COSMIC: COSV55102106;