chr2-159819916-C-G

Position:

• chr2-159819916-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LY75 NM_002349.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517

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]

ACMG classification

Verdict is Likely_benign. Variant got -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/exons	MANE	Protein	UniProt
LY75	NM_002349.4	c.3963G>C	p.Lys1321Asn	missense_variant	29/35	ENST00000263636.5	NP_002340.2
LY75-CD302	NM_001198759.1	c.3963G>C	p.Lys1321Asn	missense_variant	29/39		NP_001185688.1
LY75-CD302	NM_001198760.1	c.3963G>C	p.Lys1321Asn	missense_variant	29/38		NP_001185689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY75	ENST00000263636.5	c.3963G>C	p.Lys1321Asn	missense_variant	29/35	1	NM_002349.4	ENSP00000263636.4
LY75-CD302	ENST00000504764.5	c.3963G>C	p.Lys1321Asn	missense_variant	29/39	2		ENSP00000423463.1
LY75-CD302	ENST00000505052.1	c.3963G>C	p.Lys1321Asn	missense_variant	29/38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443316 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 717512

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.27
DEOGEN2	Benign	0.021	.;.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.17	T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.039	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.6	.;.;N
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	T
GERP RS		4.5
Varity_R		0.18
gMVP		0.33

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

Other links and lift over

dbSNP: rs12692566; hg19: chr2-160676427;