2-159819916-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_002349.4(LY75):​c.3963G>A​(p.Lys1321Lys) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LY75 NM_002349.4 synonymous
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=0.517 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY75	NM_002349.4	c.3963G>A	p.Lys1321Lys	synonymous_variant	Exon 29 of 35	ENST00000263636.5	NP_002340.2
LY75-CD302	NM_001198759.1	c.3963G>A	p.Lys1321Lys	synonymous_variant	Exon 29 of 39		NP_001185688.1
LY75-CD302	NM_001198760.1	c.3963G>A	p.Lys1321Lys	synonymous_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>A	p.Lys1321Lys	synonymous_variant	Exon 29 of 35	1	NM_002349.4	ENSP00000263636.4
LY75-CD302	ENST00000504764.5	c.3963G>A	p.Lys1321Lys	synonymous_variant	Exon 29 of 39	2		ENSP00000423463.1
LY75-CD302	ENST00000505052.1	c.3963G>A	p.Lys1321Lys	synonymous_variant	Exon 29 of 38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	4.9
DANN	Benign	0.66
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism

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;