2-159879264-C-T

Position:

• chr2-159879264-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002349.4(LY75):​c.1510G>A​(p.Asp504Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000834 in 1,611,952 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (5 hom.)
• Consequence: LY75 NM_002349.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.119

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]

LY75 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004189372).
• BP6: Variant 2-159879264-C-T is Benign according to our data. Variant chr2-159879264-C-T is described in ClinVar as [Benign]. Clinvar id is 730665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000456 (666/1459660) while in subpopulation AFR AF= 0.0168 (561/33344). AF 95% confidence interval is 0.0157. There are 5 homozygotes in gnomad4_exome. There are 273 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY75	NM_002349.4	c.1510G>A	p.Asp504Asn	missense_variant	9/35	ENST00000263636.5	NP_002340.2
LY75-CD302	NM_001198759.1	c.1510G>A	p.Asp504Asn	missense_variant	9/39		NP_001185688.1
LY75-CD302	NM_001198760.1	c.1510G>A	p.Asp504Asn	missense_variant	9/38		NP_001185689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY75	ENST00000263636.5	c.1510G>A	p.Asp504Asn	missense_variant	9/35	1	NM_002349.4	ENSP00000263636.4
LY75-CD302	ENST00000504764.5	c.1510G>A	p.Asp504Asn	missense_variant	9/39	2		ENSP00000423463.1
LY75	ENST00000484559.1	n.1570G>A		non_coding_transcript_exon_variant	9/13	1
LY75-CD302	ENST00000505052.1	c.1510G>A	p.Asp504Asn	missense_variant	9/38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes AF: 0.00445 AC: 677 AN: 152174 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

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: 0.0000441

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00114 AC: 283 AN: 248898 Hom.: 2 AF XY: 0.000818 AC XY: 110 AN XY: 134494

Gnomad AFR exome AF: 0.0157

Gnomad AMR exome AF: 0.000707

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000333

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.000456 AC: 666 AN: 1459660 Hom.: 5 Cov.: 31 AF XY: 0.000376 AC XY: 273 AN XY: 726072

Gnomad4 AFR exome AF: 0.0168

Gnomad4 AMR exome AF: 0.000792

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000467

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.000962

GnomAD4 genome AF: 0.00446 AC: 679 AN: 152292 Hom.: 7 Cov.: 32 AF XY: 0.00434 AC XY: 323 AN XY: 74466

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000703 Hom.: 2

Bravo AF: 0.00494

ESP6500AA AF: 0.0134 AC: 59

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00143 AC: 174

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.088	.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.50	T;T;T
MetaRNN	Benign	0.0042	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	.;.;L
PROVEAN	Benign	-0.58	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.081	T;T;T
Polyphen		0.018	.;.;B
Vest4		0.14
MVP		0.13
MPC		0.049
ClinPred		0.0036	T
GERP RS		2.4
Varity_R		0.090
gMVP		0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs77761086; hg19: chr2-160735775;