chr2-159879291-C-T

Position:

• chr2-159879291-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002349.4(LY75):​c.1483G>A​(p.Ala495Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,613,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: LY75 NM_002349.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.602

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]

LY75 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.00241673).
• BP6: Variant 2-159879291-C-T is Benign according to our data. Variant chr2-159879291-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 721813.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY75	NM_002349.4	c.1483G>A	p.Ala495Thr	missense_variant	9/35	ENST00000263636.5	NP_002340.2
LY75-CD302	NM_001198759.1	c.1483G>A	p.Ala495Thr	missense_variant	9/39		NP_001185688.1
LY75-CD302	NM_001198760.1	c.1483G>A	p.Ala495Thr	missense_variant	9/38		NP_001185689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY75	ENST00000263636.5	c.1483G>A	p.Ala495Thr	missense_variant	9/35	1	NM_002349.4	ENSP00000263636.4
LY75-CD302	ENST00000504764.5	c.1483G>A	p.Ala495Thr	missense_variant	9/39	2		ENSP00000423463.1
LY75	ENST00000484559.1	n.1543G>A		non_coding_transcript_exon_variant	9/13	1
LY75-CD302	ENST00000505052.1	c.1483G>A	p.Ala495Thr	missense_variant	9/38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 158 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00355

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000327 AC: 82 AN: 250586 Hom.: 0 AF XY: 0.000258 AC XY: 35 AN XY: 135446

Gnomad AFR exome AF: 0.00363

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000971

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000136 AC: 199 AN: 1461298 Hom.: 0 Cov.: 31 AF XY: 0.000122 AC XY: 89 AN XY: 726952

Gnomad4 AFR exome AF: 0.00380

Gnomad4 AMR exome AF: 0.000336

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.0000342

Gnomad4 OTH exome AF: 0.000199

GnomAD4 genome AF: 0.00104 AC: 159 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.00113 AC XY: 84 AN XY: 74460

Gnomad4 AFR AF: 0.00356

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.00130

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000371 AC: 45

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0050
DANN	Benign	0.49
DEOGEN2	Benign	0.050	.;.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.0024	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.95	.;.;N
PROVEAN	Benign	0.39	N;N;N
REVEL	Benign	0.035
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0020	.;.;B
Vest4		0.019
MVP		0.014
MPC		0.049
ClinPred		0.0080	T
GERP RS		-11
Varity_R		0.030
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs114320498; hg19: chr2-160735802;