chr2-159882292-G-A

Position:

• chr2-159882292-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002349.4(LY75):​c.1078C>T​(p.Arg360Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,804 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (5 hom.)
• Consequence: LY75 NM_002349.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.62

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013620734).
• BP6: Variant 2-159882292-G-A is Benign according to our data. Variant chr2-159882292-G-A is described in ClinVar as [Benign]. Clinvar id is 730667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY75	NM_002349.4	c.1078C>T	p.Arg360Cys	missense_variant	7/35	ENST00000263636.5	NP_002340.2
LY75-CD302	NM_001198759.1	c.1078C>T	p.Arg360Cys	missense_variant	7/39		NP_001185688.1
LY75-CD302	NM_001198760.1	c.1078C>T	p.Arg360Cys	missense_variant	7/38		NP_001185689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY75	ENST00000263636.5	c.1078C>T	p.Arg360Cys	missense_variant	7/35	1	NM_002349.4	ENSP00000263636.4
LY75-CD302	ENST00000504764.5	c.1078C>T	p.Arg360Cys	missense_variant	7/39	2		ENSP00000423463.1
LY75	ENST00000484559.1	n.1138C>T		non_coding_transcript_exon_variant	7/13	1
LY75-CD302	ENST00000505052.1	c.1078C>T	p.Arg360Cys	missense_variant	7/38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes AF: 0.00385 AC: 586 AN: 152184 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00161 AC: 404 AN: 250666 Hom.: 2 AF XY: 0.00147 AC XY: 199 AN XY: 135464

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.000724

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00160

Gnomad FIN exome AF: 0.00107

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.00146 AC: 2130 AN: 1461502 Hom.: 5 Cov.: 31 AF XY: 0.00138 AC XY: 1006 AN XY: 727060

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.000761

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00166

Gnomad4 FIN exome AF: 0.000937

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00385 AC: 586 AN: 152302 Hom.: 3 Cov.: 33 AF XY: 0.00357 AC XY: 266 AN XY: 74466

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00135

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00170 Hom.: 2

Bravo AF: 0.00400

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00999 AC: 44

ESP6500EA AF: 0.00186 AC: 16

ExAC AF: 0.00196 AC: 238

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.000949

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	.;.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.91	D;D;D
MetaRNN	Benign	0.014	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	.;.;M
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Benign	0.15
Sift	Benign	0.043	D;D;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.35
MVP		0.26
MPC		0.24
ClinPred		0.038	T
GERP RS		5.6
Varity_R		0.11
gMVP		0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs35675007; hg19: chr2-160738803; COSMIC: COSV55108133;