Genetic Variant LY75:p.Lys1321Asn (chr2-159819916-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002349.4(LY75):c.3963G>C(p.Lys1321Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LY75
NM_002349.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.517

Publications

42 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039389104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
LY75	NM_002349.4 link	c.3963G>C	p.Lys1321Asn	missense_variant	Exon 29 of 35	ENST00000263636.5	NP_002340.2
LY75-CD302	NM_001198759.1 link	c.3963G>C	p.Lys1321Asn	missense_variant	Exon 29 of 39		NP_001185688.1
LY75-CD302	NM_001198760.1 link	c.3963G>C	p.Lys1321Asn	missense_variant	Exon 29 of 38		NP_001185689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
LY75	ENST00000263636.5 link	c.3963G>C	p.Lys1321Asn	missense_variant	Exon 29 of 35	1	NM_002349.4	ENSP00000263636.4
LY75-CD302	ENST00000504764.5 link	c.3963G>C	p.Lys1321Asn	missense_variant	Exon 29 of 39	2		ENSP00000423463.1
LY75-CD302	ENST00000505052.1 link	c.3963G>C	p.Lys1321Asn	missense_variant	Exon 29 of 38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1443316

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717512

African (AFR)

AF:

0.00

AC:

AN:

32180

American (AMR)

AF:

0.00

AC:

AN:

39608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25056

East Asian (EAS)

AF:

0.00

AC:

AN:

39514

South Asian (SAS)

AF:

0.00

AC:

AN:

82170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106608

Other (OTH)

AF:

0.00

AC:

AN:

59438

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.021

.;.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.17

T;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.6

.;.;N

PhyloP100

0.52

PROVEAN

Benign

1.9

N;N;N

REVEL

Benign

0.079

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.053

MutPred

0.56

Loss of ubiquitination at K1321 (P = 0.0155);Loss of ubiquitination at K1321 (P = 0.0155);Loss of ubiquitination at K1321 (P = 0.0155);

MVP

0.030

MPC

0.055

ClinPred

0.13

GERP RS

4.5

Varity_R

0.18

gMVP

0.33

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over