2-159878680-C-A

Position:

chr2-159878680-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002349.4(LY75):c.1557G>T(p.Glu519Asp) 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 1,613,926 control chromosomes in the GnomAD database, including 44 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 0.011 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 25 hom. )

Consequence

LY75
NM_002349.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.718

Variant links:

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 links:

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-CD302 links:

LY75 (HGNC:):

LY75 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002149552).

BP6

Variant 2-159878680-C-A is Benign according to our data. Variant chr2-159878680-C-A is described in ClinVar as [Benign]. Clinvar id is 791874.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 (1648/152282) while in subpopulation AFR AF= 0.0379 (1574/41568). 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 linkuse as main transcript	c.1557G>T	p.Glu519Asp	missense_variant	10/35	ENST00000263636.5	NP_002340.2	O60449-1Q59H44
LY75-CD302	NM_001198759.1 linkuse as main transcript	c.1557G>T	p.Glu519Asp	missense_variant	10/39		NP_001185688.1	O60449-2
LY75-CD302	NM_001198760.1 linkuse as main transcript	c.1557G>T	p.Glu519Asp	missense_variant	10/38		NP_001185689.1	O60449-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LY75	ENST00000263636.5 linkuse as main transcript	c.1557G>T	p.Glu519Asp	missense_variant	10/35	1	NM_002349.4	ENSP00000263636.4	O60449-1
LY75-CD302	ENST00000504764.5 linkuse as main transcript	c.1557G>T	p.Glu519Asp	missense_variant	10/39	2		ENSP00000423463.1
LY75	ENST00000484559.1 linkuse as main transcript	n.1617G>T		non_coding_transcript_exon_variant	10/13	1
LY75-CD302	ENST00000505052.1 linkuse as main transcript	c.1557G>T	p.Glu519Asp	missense_variant	10/38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1644

AN:

152164

Hom.:

Cov.:

show subpopulations

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:

0.00719

GnomAD3 exomes

AF:

0.00273

AC:

686

AN:

251240

Hom.:

AF XY:

0.00203

AC XY:

276

AN XY:

135788

show subpopulations

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:

1491

AN:

1461644

Hom.:

Cov.:

AF XY:

0.000839

AC XY:

610

AN XY:

727120

show subpopulations

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:

0.0000225

Gnomad4 OTH exome

AF:

0.00224

GnomAD4 genome

AF:

0.0108

AC:

1648

AN:

152282

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

793

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0379

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:

0.00712

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.0120

ESP6500AA

AF:

0.0361

AC:

159

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00344

AC:

418

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.00

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

0.13

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.089

.;.;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.50

T;T;T

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;.;L

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.041

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.43

T;T;T

Polyphen

0.34

.;.;B

Vest4

0.19

MutPred

0.47

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.15

MPC

0.052

ClinPred

0.00061

GERP RS

-1.0

Varity_R

0.13

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over