rs509749

Variant names:

• chr1-160823770-A-G
• rs509749
• NM_002348.4:c.1804A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002348.4(LY9):​c.1804A>G​(p.Met602Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,612,540 control chromosomes in the GnomAD database, including 190,105 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M602T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.55 (24822 hom., cov: 31)
  • Exomes 𝑓: 0.47 (165283 hom.)
• Consequence: LY9 NM_002348.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.201
• Publications: 57 publications found

Genes affected

LY9 (HGNC:6730): (lymphocyte antigen 9) LY9 belongs to the SLAM family of immunomodulatory receptors (see SLAMF1; MIM 603492) and interacts with the adaptor molecule SAP (SH2D1A; MIM 300490) (Graham et al., 2006 [PubMed 16365421]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0925713E-6).
• BP6: Variant 1-160823770-A-G is Benign according to our data. Variant chr1-160823770-A-G is described in ClinVar as Benign. ClinVar VariationId is 1242630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY9	NM_002348.4	c.1804A>G	p.Met602Val	missense_variant	Exon 8 of 10	ENST00000263285.11	NP_002339.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY9	ENST00000263285.11	c.1804A>G	p.Met602Val	missense_variant	Exon 8 of 10	1	NM_002348.4	ENSP00000263285.5
LY9	ENST00000368037.10	c.1762A>G	p.Met588Val	missense_variant	Exon 8 of 10	1		ENSP00000357016.5
LY9	ENST00000392203.8	c.1534A>G	p.Met512Val	missense_variant	Exon 7 of 9	1		ENSP00000376039.4
LY9	ENST00000368035.1	c.928A>G	p.Met310Val	missense_variant	Exon 5 of 6	1		ENSP00000357014.2

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83909 AN: 151888 Hom.: 24766 Cov.: 31

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.553

GnomAD2 exomes AF: 0.541 AC: 135172 AN: 249956 AF XY: 0.530

Gnomad AFR exome AF: 0.756

Gnomad AMR exome AF: 0.719

Gnomad ASJ exome AF: 0.516

Gnomad EAS exome AF: 0.727

Gnomad FIN exome AF: 0.471

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.511

GnomAD4 exome AF: 0.465 AC: 679496 AN: 1460534 Hom.: 165283 Cov.: 38 AF XY: 0.467 AC XY: 339344 AN XY: 726612

African (AFR) AF: 0.760 AC: 25413 AN: 33460

American (AMR) AF: 0.706 AC: 31580 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 13399 AN: 26126

East Asian (EAS) AF: 0.739 AC: 29313 AN: 39682

South Asian (SAS) AF: 0.597 AC: 51505 AN: 86230

European-Finnish (FIN) AF: 0.473 AC: 25228 AN: 53392

Middle Eastern (MID) AF: 0.474 AC: 2732 AN: 5764

European-Non Finnish (NFE) AF: 0.423 AC: 470152 AN: 1110826

Other (OTH) AF: 0.500 AC: 30174 AN: 60338

GnomAD4 genome AF: 0.553 AC: 84024 AN: 152006 Hom.: 24822 Cov.: 31 AF XY: 0.556 AC XY: 41287 AN XY: 74304

African (AFR) AF: 0.750 AC: 31082 AN: 41452

American (AMR) AF: 0.604 AC: 9230 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3468

East Asian (EAS) AF: 0.705 AC: 3642 AN: 5164

South Asian (SAS) AF: 0.619 AC: 2985 AN: 4824

European-Finnish (FIN) AF: 0.460 AC: 4853 AN: 10542

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28946 AN: 67960

Other (OTH) AF: 0.553 AC: 1168 AN: 2114

Alfa AF: 0.472 Hom.: 81097

Bravo AF: 0.572

TwinsUK AF: 0.426 AC: 1579

ALSPAC AF: 0.421 AC: 1624

ESP6500AA AF: 0.736 AC: 3241

ESP6500EA AF: 0.422 AC: 3625

ExAC AF: 0.538 AC: 65332

Asia WGS AF: 0.710 AC: 2472 AN: 3478

EpiCase AF: 0.424

EpiControl AF: 0.426

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26221972) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.023
DANN	Benign	0.17
DEOGEN2	Benign	0.026	.;.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.10	T;T;T
MetaRNN	Benign	0.0000021	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	.;.;N
PhyloP100		-0.20
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.50	.;.;N
REVEL	Benign	0.041
Sift	Benign	1.0	.;.;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.020
MPC		0.059
ClinPred		0.00030	T
GERP RS		2.3
Varity_R		0.040
gMVP		0.051
Mutation Taster		=100/0	polymorphism (auto)

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: rs509749; hg19: chr1-160793560; COSMIC: COSV54431599;