2-159878679-C-A

Variant names:

• chr2-159878679-C-A
• rs115254354
• NM_002349.4:c.1558G>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002349.4(LY75):​c.1558G>T​(p.Asp520Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,613,968 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (25 hom.)
• Consequence: LY75 NM_002349.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.99
• Publications: 3 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 2-159878679-C-A is Benign according to our data. Variant chr2-159878679-C-A is described in ClinVar as Benign. ClinVar VariationId is 791873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0108 (1647/152314) while in subpopulation AFR AF = 0.0378 (1573/41564). AF 95% confidence interval is 0.0363. There are 19 homozygotes in GnomAd4. There are 793 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

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.1558G>T	p.Asp520Tyr	missense	Exon 10 of 35	NP_002340.2	O60449-1
	LY75-CD302	NM_001198759.1		c.1558G>T	p.Asp520Tyr	missense	Exon 10 of 39	NP_001185688.1	O60449-2
	LY75-CD302	NM_001198760.1		c.1558G>T	p.Asp520Tyr	missense	Exon 10 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.1558G>T	p.Asp520Tyr	missense	Exon 10 of 35	ENSP00000263636.4	O60449-1
	LY75-CD302	ENST00000504764.5	TSL:2	c.1558G>T	p.Asp520Tyr	missense	Exon 10 of 39	ENSP00000423463.1
	LY75	ENST00000484559.1	TSL:1	n.1618G>T		non_coding_transcript_exon	Exon 10 of 13

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1643 AN: 152196 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00716

GnomAD2 exomes AF: 0.00273 AC: 686 AN: 251244 AF XY: 0.00203

Gnomad AFR exome AF: 0.0390

Gnomad AMR exome AF: 0.000984

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.00102 AC: 1489 AN: 1461654 Hom.: 25 Cov.: 32 AF XY: 0.000838 AC XY: 609 AN XY: 727120

African (AFR) AF: 0.0373 AC: 1246 AN: 33440

American (AMR) AF: 0.00154 AC: 69 AN: 44708

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5764

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111904

Other (OTH) AF: 0.00224 AC: 135 AN: 60378

GnomAD4 genome AF: 0.0108 AC: 1647 AN: 152314 Hom.: 19 Cov.: 32 AF XY: 0.0106 AC XY: 793 AN XY: 74484

African (AFR) AF: 0.0378 AC: 1573 AN: 41564

American (AMR) AF: 0.00347 AC: 53 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00422 Hom.: 28

Bravo AF: 0.0120

ESP6500AA AF: 0.0361 AC: 159

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00344 AC: 418

Asia WGS AF: 0.00231 AC: 8 AN: 3476

EpiCase AF: 0.00

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	-0.089
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.0
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.071
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.027	D
Polyphen		0.98	D
Vest4		0.53
MVP		0.25
MPC		0.12
ClinPred		0.035	T
GERP RS		2.3
Varity_R		0.22
gMVP		0.59
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.29		Position offset: 42

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

Other links and lift over

dbSNP: rs115254354; hg19: chr2-160735190;