chr19-54507942-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAIR2	NM_002288.6	c.122C>G	p.Pro41Arg	missense_variant	Exon 3 of 5	ENST00000301202.7	NP_002279.2
LAIR2	NM_021270.5	c.122C>G	p.Pro41Arg	missense_variant	Exon 3 of 4		NP_067154.1
LAIR2	XM_011526961.3	c.86C>G	p.Pro29Arg	missense_variant	Exon 2 of 4		XP_011525263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAIR2	ENST00000301202.7	c.122C>G	p.Pro41Arg	missense_variant	Exon 3 of 5	1	NM_002288.6	ENSP00000301202.2
LAIR2	ENST00000351841.2	c.122C>G	p.Pro41Arg	missense_variant	Exon 3 of 4	1		ENSP00000301203.2
LAIR2	ENST00000412608.5	c.104C>G	p.Pro35Arg	missense_variant	Exon 3 of 3	1		ENSP00000390729.1
LAIR2	ENST00000610651.1	c.68C>G	p.Pro23Arg	missense_variant	Exon 2 of 2	5		ENSP00000484484.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	.;.;N;N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	1.0	N;.;N;N
REVEL	Benign	0.043
Sift	Benign	0.98	T;.;T;T
Sift4G	Benign	0.87	T;T;T;T
Polyphen		0.0010	B;.;B;B
Vest4		0.069, 0.090
MutPred		0.32		.;.;Gain of methylation at P41 (P = 0.0141);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55019157;