2-159878677-ATC-GTG

Variant names:

• chr2-159878677-ATC-GTG
• NM_002349.4:c.1558_1560delGATinsCAC
• LY75 p.Asp520His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002349.4(LY75):​c.1558_1560delGATinsCAC​(p.Asp520His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. D520Y) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LY75 NM_002349.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.1558_1560delGATinsCAC	p.Asp520His	missense	N/A	NP_002340.2	O60449-1
	LY75-CD302	NM_001198759.1		c.1558_1560delGATinsCAC	p.Asp520His	missense	N/A	NP_001185688.1	O60449-2
	LY75-CD302	NM_001198760.1		c.1558_1560delGATinsCAC	p.Asp520His	missense	N/A	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.1558_1560delGATinsCAC	p.Asp520His	missense	N/A	ENSP00000263636.4	O60449-1
	LY75-CD302	ENST00000504764.5	TSL:2	c.1558_1560delGATinsCAC	p.Asp520His	missense	N/A	ENSP00000423463.1
	LY75	ENST00000484559.1	TSL:1	n.1618_1620delGATinsCAC		non_coding_transcript_exon	Exon 10 of 13

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-160735188;