2-159850420-G-A

Variant names:

• chr2-159850420-G-A
• rs149297961
• NM_002349.4:c.2931C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_002349.4(LY75):​c.2931C>T​(p.Ser977Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,550 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000031 (1 hom.)
• Consequence: LY75 NM_002349.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• Publications: 5 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.89 with no splicing effect.

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.2931C>T	p.Ser977Ser	synonymous	Exon 22 of 35	NP_002340.2	O60449-1
	LY75-CD302	NM_001198759.1		c.2931C>T	p.Ser977Ser	synonymous	Exon 22 of 39	NP_001185688.1	O60449-2
	LY75-CD302	NM_001198760.1		c.2931C>T	p.Ser977Ser	synonymous	Exon 22 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.2931C>T	p.Ser977Ser	synonymous	Exon 22 of 35	ENSP00000263636.4	O60449-1
	LY75-CD302	ENST00000504764.5	TSL:2	c.2931C>T	p.Ser977Ser	synonymous	Exon 22 of 39	ENSP00000423463.1
	LY75-CD302	ENST00000505052.1	TSL:2	c.2931C>T	p.Ser977Ser	synonymous	Exon 22 of 38	ENSP00000421035.1

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 151972 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000797 AC: 20 AN: 250968 AF XY: 0.0000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000308 AC: 45 AN: 1461460 Hom.: 1 Cov.: 31 AF XY: 0.0000330 AC XY: 24 AN XY: 727040

African (AFR) AF: 0.0000299 AC: 1 AN: 33464

American (AMR) AF: 0.000470 AC: 21 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111686

Other (OTH) AF: 0.0000497 AC: 3 AN: 60382

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152090 Hom.: 0 Cov.: 31 AF XY: 0.000403 AC XY: 30 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41506

American (AMR) AF: 0.00229 AC: 35 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000155

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.24
DANN	Benign	0.36
PhyloP100		-0.89
Mutation Taster		=100/0	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: rs149297961; hg19: chr2-160706931; COSMIC: COSV55108386;