rs114924959

Variant names:

• chr2-159850034-C-T
• rs114924959
• NM_002349.4:c.3096G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-159850034-C-T
• chr2-159850034-C-A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002349.4(LY75):​c.3096G>A​(p.Thr1032Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,613,958 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0024 (7 hom.)
• Consequence: LY75 NM_002349.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56
• Publications: 2 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 2-159850034-C-T is Benign according to our data. Variant chr2-159850034-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2651460.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.56 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

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.3096G>A	p.Thr1032Thr	synonymous	Exon 23 of 35	NP_002340.2	O60449-1
	LY75-CD302	NM_001198759.1		c.3096G>A	p.Thr1032Thr	synonymous	Exon 23 of 39	NP_001185688.1	O60449-2
	LY75-CD302	NM_001198760.1		c.3096G>A	p.Thr1032Thr	synonymous	Exon 23 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.3096G>A	p.Thr1032Thr	synonymous	Exon 23 of 35	ENSP00000263636.4	O60449-1
	LY75-CD302	ENST00000504764.5	TSL:2	c.3096G>A	p.Thr1032Thr	synonymous	Exon 23 of 39	ENSP00000423463.1
	LY75-CD302	ENST00000505052.1	TSL:2	c.3096G>A	p.Thr1032Thr	synonymous	Exon 23 of 38	ENSP00000421035.1

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 219 AN: 152152 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000773

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00138 AC: 346 AN: 251084 AF XY: 0.00150

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00243 AC: 3547 AN: 1461688 Hom.: 7 Cov.: 31 AF XY: 0.00229 AC XY: 1664 AN XY: 727136

African (AFR) AF: 0.000538 AC: 18 AN: 33476

American (AMR) AF: 0.00235 AC: 105 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86242

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53412

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.00292 AC: 3244 AN: 1111900

Other (OTH) AF: 0.00227 AC: 137 AN: 60386

GnomAD4 genome AF: 0.00144 AC: 219 AN: 152270 Hom.: 0 Cov.: 31 AF XY: 0.00129 AC XY: 96 AN XY: 74460

African (AFR) AF: 0.000770 AC: 32 AN: 41534

American (AMR) AF: 0.00170 AC: 26 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00223 AC: 152 AN: 68024

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00137 Hom.: 0

Bravo AF: 0.00164

EpiCase AF: 0.00213

EpiControl AF: 0.00302

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
BayesDel_noAF	Benign	-0.51
CADD	Benign	4.5
DANN	Benign	0.57
PhyloP100		-1.6
Mutation Taster		=99/1	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: rs114924959; hg19: chr2-160706545; COSMIC: COSV55110024;