rs201955061

Variant names:

• chr19-54507942-C-G
• rs201955061
• NM_002288.6:c.122C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-54507942-C-G
• chr19-54507942-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002288.6(LAIR2):​c.122C>G​(p.Pro41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P41L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LAIR2 NM_002288.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.90
• Publications: 0 publications found

Genes affected

LAIR2 (HGNC:6478): (leukocyte associated immunoglobulin like receptor 2) The protein encoded by this gene is a member of the immunoglobulin superfamily. It was identified by its similarity to leukocyte-associated immunoglobulin-like receptor 1, a membrane-bound receptor that modulates innate immune response. The protein encoded by this locus is a soluble receptor that may play roles in both inhibition of collagen-induced platelet aggregation and vessel formation during placental implantation. This gene maps to a region of 19q13.4, termed the leukocyte receptor cluster, which contains 29 genes in the immunoglobulin superfamily. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039187998).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002288.6. 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
	LAIR2	NM_002288.6	MANE Select	c.122C>G	p.Pro41Arg	missense	Exon 3 of 5	NP_002279.2
	LAIR2	NM_021270.5		c.122C>G	p.Pro41Arg	missense	Exon 3 of 4	NP_067154.1	Q6ISS4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAIR2	ENST00000301202.7	TSL:1 MANE Select	c.122C>G	p.Pro41Arg	missense	Exon 3 of 5	ENSP00000301202.2	Q6ISS4-1
	LAIR2	ENST00000351841.2	TSL:1	c.122C>G	p.Pro41Arg	missense	Exon 3 of 4	ENSP00000301203.2	Q6ISS4-2
	LAIR2	ENST00000412608.5	TSL:1	c.104C>G	p.Pro35Arg	missense	Exon 3 of 3	ENSP00000390729.1	C9JFQ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.0010
DANN	Benign	0.18
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0041	N
M_CAP	Benign	0.00073	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N
PhyloP100		-4.9
PrimateAI	Benign	0.18	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.043
Sift	Benign	0.98	T
Sift4G	Benign	0.87	T
Polyphen		0.0010	B
Vest4		0.069
MutPred		0.32		Gain of methylation at P41 (P = 0.0141)
MVP		0.16
MPC		0.23
ClinPred		0.034	T
GERP RS		-6.8
Varity_R		0.061
gMVP		0.14
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: rs201955061; hg19: chr19-55019157;