2-159872571-A-G

Variant names:

Variant summary

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

The NM_002349.4(LY75):c.1997T>C(p.Val666Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,613,756 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.011 ( 29 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 24 hom. )

Consequence

LY75
NM_002349.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.36

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:

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=0.003575623).

BP6

Variant 2-159872571-A-G is Benign according to our data. Variant chr2-159872571-A-G is described in ClinVar as [Benign]. Clinvar id is 791153.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 = 0.011 (1671/152294) while in subpopulation AFR AF= 0.0375 (1559/41564). AF 95% confidence interval is 0.036. There are 29 homozygotes in gnomad4. There are 795 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY75	NM_002349.4 link	c.1997T>C	p.Val666Ala	missense_variant	Exon 13 of 35	ENST00000263636.5	NP_002340.2	O60449-1Q59H44
LY75-CD302	NM_001198759.1 link	c.1997T>C	p.Val666Ala	missense_variant	Exon 13 of 39		NP_001185688.1	O60449-2
LY75-CD302	NM_001198760.1 link	c.1997T>C	p.Val666Ala	missense_variant	Exon 13 of 38		NP_001185689.1	O60449-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LY75	ENST00000263636.5 link	c.1997T>C	p.Val666Ala	missense_variant	Exon 13 of 35	1	NM_002349.4	ENSP00000263636.4	O60449-1
LY75-CD302	ENST00000504764.5 link	c.1997T>C	p.Val666Ala	missense_variant	Exon 13 of 39	2		ENSP00000423463.1
LY75	ENST00000484559.1 link	n.2057T>C		non_coding_transcript_exon_variant	Exon 13 of 13	1
LY75-CD302	ENST00000505052.1 link	c.1997T>C	p.Val666Ala	missense_variant	Exon 13 of 38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1657

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0373

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00277

AC:

694

AN:

250910

Hom.:

AF XY:

0.00195

AC XY:

265

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.0392

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00116

AC:

1696

AN:

1461462

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

728

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.0423

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.0110

AC:

1671

AN:

152294

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

795

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0375

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.0133

ESP6500AA

AF:

0.0388

AC:

171

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00325

AC:

395

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

.;.;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.0083

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;.;M

PROVEAN

Benign

-0.67

N;N;N

REVEL

Benign

0.086

Sift

Benign

0.065

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.065

.;.;B

Vest4

0.10

MVP

0.072

MPC

0.33

ClinPred

0.025

GERP RS

4.9

Varity_R

0.11

gMVP

0.29

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

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