chr2-159850420-G-T

Position:

• chr2-159850420-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002349.4(LY75):​c.2931C>A​(p.Ser977Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,613,550 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00040 (1 hom.)
• Consequence: LY75 NM_002349.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.890

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042654037).
• BP6: Variant 2-159850420-G-T is Benign according to our data. Variant chr2-159850420-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651461.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY75	NM_002349.4	c.2931C>A	p.Ser977Arg	missense_variant	22/35	ENST00000263636.5	NP_002340.2
LY75-CD302	NM_001198759.1	c.2931C>A	p.Ser977Arg	missense_variant	22/39		NP_001185688.1
LY75-CD302	NM_001198760.1	c.2931C>A	p.Ser977Arg	missense_variant	22/38		NP_001185689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY75	ENST00000263636.5	c.2931C>A	p.Ser977Arg	missense_variant	22/35	1	NM_002349.4	ENSP00000263636.4
LY75-CD302	ENST00000504764.5	c.2931C>A	p.Ser977Arg	missense_variant	22/39	2		ENSP00000423463.1
LY75-CD302	ENST00000505052.1	c.2931C>A	p.Ser977Arg	missense_variant	22/38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes AF: 0.000349 AC: 53 AN: 151972 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000295 AC: 74 AN: 250968 Hom.: 1 AF XY: 0.000302 AC XY: 41 AN XY: 135614

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000538

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000400 AC: 585 AN: 1461460 Hom.: 1 Cov.: 31 AF XY: 0.000384 AC XY: 279 AN XY: 727040

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000478

Gnomad4 OTH exome AF: 0.000364

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152090 Hom.: 0 Cov.: 31 AF XY: 0.000390 AC XY: 29 AN XY: 74362

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000478 Hom.: 0

Bravo AF: 0.000261

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000313 AC: 38

EpiCase AF: 0.000818

EpiControl AF: 0.000535

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

LY75: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.068
DANN	Benign	0.95
DEOGEN2	Benign	0.026	.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	.;.;N
PROVEAN	Benign	-0.43	N;N;N
REVEL	Benign	0.053
Sift	Benign	0.046	D;D;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		0.78	.;.;P
Vest4		0.35
MutPred		0.49		Loss of disorder (P = 0.0659);Loss of disorder (P = 0.0659);Loss of disorder (P = 0.0659);
MVP		0.030
MPC		0.34
ClinPred		0.041	T
GERP RS		-7.9
Varity_R		0.11
gMVP		0.57

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: rs149297961; hg19: chr2-160706931;