chr2-159878679-C-A

Position:

• chr2-159878679-C-A

Variant summary

Our verdict is Benign. Variant got -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

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.

• BP6: Variant 2-159878679-C-A is Benign according to our data. Variant chr2-159878679-C-A is described in ClinVar as [Benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY75	NM_002349.4	c.1558G>T	p.Asp520Tyr	missense_variant	10/35	ENST00000263636.5	NP_002340.2
LY75-CD302	NM_001198759.1	c.1558G>T	p.Asp520Tyr	missense_variant	10/39		NP_001185688.1
LY75-CD302	NM_001198760.1	c.1558G>T	p.Asp520Tyr	missense_variant	10/38		NP_001185689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY75	ENST00000263636.5	c.1558G>T	p.Asp520Tyr	missense_variant	10/35	1	NM_002349.4	ENSP00000263636.4
LY75-CD302	ENST00000504764.5	c.1558G>T	p.Asp520Tyr	missense_variant	10/39	2		ENSP00000423463.1
LY75	ENST00000484559.1	n.1618G>T		non_coding_transcript_exon_variant	10/13	1
LY75-CD302	ENST00000505052.1	c.1558G>T	p.Asp520Tyr	missense_variant	10/38	2		ENSP00000421035.1

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

GnomAD3 exomes AF: 0.00273 AC: 686 AN: 251244 Hom.: 14 AF XY: 0.00203 AC XY: 276 AN XY: 135792

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 SAS exome AF: 0.0000653

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

Gnomad4 AFR exome AF: 0.0373

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00224

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

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.00182 Hom.: 10

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

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	Dec 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

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;D;D
MetaRNN	Benign	0.0048	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	.;.;M
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Benign	0.071
Sift	Uncertain	0.016	D;D;D
Sift4G	Uncertain	0.027	D;D;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs115254354; hg19: chr2-160735190;