chr2-159879291-C-G

Variant names:

• chr2-159879291-C-G
• rs114320498
• NM_002349.4:c.1483G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002349.4(LY75):​c.1483G>C​(p.Ala495Pro) 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. A495T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LY75 NM_002349.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06242618).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY75	NM_002349.4	MANE Select	c.1483G>C	p.Ala495Pro	missense	Exon 9 of 35	NP_002340.2	O60449-1
	LY75-CD302	NM_001198759.1		c.1483G>C	p.Ala495Pro	missense	Exon 9 of 39	NP_001185688.1	O60449-2
	LY75-CD302	NM_001198760.1		c.1483G>C	p.Ala495Pro	missense	Exon 9 of 38	NP_001185689.1	O60449-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY75	ENST00000263636.5	TSL:1 MANE Select	c.1483G>C	p.Ala495Pro	missense	Exon 9 of 35	ENSP00000263636.4	O60449-1
	LY75-CD302	ENST00000504764.5	TSL:2	c.1483G>C	p.Ala495Pro	missense	Exon 9 of 39	ENSP00000423463.1
	LY75	ENST00000484559.1	TSL:1	n.1543G>C		non_coding_transcript_exon	Exon 9 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.025
DANN	Benign	0.81
DEOGEN2	Benign	0.077	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.79	N
PhyloP100		-0.60
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.042
Sift	Benign	0.15	T
Sift4G	Benign	0.10	T
Polyphen		0.76	P
Vest4		0.087
MutPred		0.45		Gain of catalytic residue at A495 (P = 0.0459)
MVP		0.030
MPC		0.13
ClinPred		0.063	T
GERP RS		-11
Varity_R		0.086
gMVP		0.49
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs114320498; hg19: chr2-160735802;