rs149297961

Variant names:

• chr2-159850420-G-T
• rs149297961
• NM_002349.4:c.2931C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-159850420-G-T
• chr2-159850420-G-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. 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. 16/21 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
• Publications: 5 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• 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 VariationId is 2651461.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY75	NM_002349.4	MANE Select	c.2931C>A	p.Ser977Arg	missense	Exon 22 of 35	NP_002340.2	O60449-1
	LY75-CD302	NM_001198759.1		c.2931C>A	p.Ser977Arg	missense	Exon 22 of 39	NP_001185688.1	O60449-2
	LY75-CD302	NM_001198760.1		c.2931C>A	p.Ser977Arg	missense	Exon 22 of 38	NP_001185689.1	O60449-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY75	ENST00000263636.5	TSL:1 MANE Select	c.2931C>A	p.Ser977Arg	missense	Exon 22 of 35	ENSP00000263636.4	O60449-1
	LY75-CD302	ENST00000504764.5	TSL:2	c.2931C>A	p.Ser977Arg	missense	Exon 22 of 39	ENSP00000423463.1
	LY75-CD302	ENST00000505052.1	TSL:2	c.2931C>A	p.Ser977Arg	missense	Exon 22 of 38	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

GnomAD2 exomes AF: 0.000295 AC: 74 AN: 250968 AF XY: 0.000302

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 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

African (AFR) AF: 0.000209 AC: 7 AN: 33464

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000478 AC: 531 AN: 1111686

Other (OTH) AF: 0.000364 AC: 22 AN: 60382

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

African (AFR) AF: 0.0000723 AC: 3 AN: 41506

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000662 AC: 45 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000473 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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	N
PhyloP100		-0.89
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.053
Sift	Benign	0.046	D
Sift4G	Uncertain	0.022	D
Polyphen		0.78	P
Vest4		0.35
MutPred		0.49		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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs149297961; hg19: chr2-160706931;