2-96739703-G-A

Variant names:

• chr2-96739703-G-A
• rs2271893
• NM_030805.4:c.187+151C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030805.4(LMAN2L):​c.187+151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 755,152 control chromosomes in the GnomAD database, including 30,863 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (5294 hom., cov: 31)
  • Exomes 𝑓: 0.28 (25569 hom.)
• Consequence: LMAN2L NM_030805.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 37 publications found

Genes affected

LMAN2L (HGNC:19263): (lectin, mannose binding 2 like) This gene encodes a protein belonging to the L-type lectin group of type 1 membrane proteins, which function in the mammalian early secretory pathway. These proteins contain luminal carbohydrate recognition domains, which display homology to leguminous lectins. Unlike other proteins of the group, which cycle in the early secretory pathway and are predominantly associated with post endoplasmic reticulum membranes, the protein encoded by this gene is a non-cycling resident protein of the ER, where it functions as a cargo receptor for glycoproteins. It is proposed to regulate exchange of folded proteins for transport to the Golgi and exchange of misfolded glycoproteins for transport to the ubiquitin-proteasome pathway. [provided by RefSeq, Apr 2016]

LMAN2L Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual developmental disorder, autosomal dominant 69

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• intellectual disability, autosomal recessive 52

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMAN2L	NM_030805.4	c.187+151C>T		intron_variant	Intron 1 of 7	ENST00000264963.9	NP_110432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMAN2L	ENST00000264963.9	c.187+151C>T		intron_variant	Intron 1 of 7	1	NM_030805.4	ENSP00000264963.4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34628 AN: 151750 Hom.: 5298 Cov.: 31

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.275 AC: 165968 AN: 603284 Hom.: 25569 AF XY: 0.270 AC XY: 85075 AN XY: 315614

African (AFR) AF: 0.0527 AC: 852 AN: 16160

American (AMR) AF: 0.170 AC: 4607 AN: 27034

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 2999 AN: 16102

East Asian (EAS) AF: 0.201 AC: 6480 AN: 32182

South Asian (SAS) AF: 0.140 AC: 7781 AN: 55688

European-Finnish (FIN) AF: 0.438 AC: 13796 AN: 31488

Middle Eastern (MID) AF: 0.135 AC: 316 AN: 2346

European-Non Finnish (NFE) AF: 0.311 AC: 121562 AN: 390754

Other (OTH) AF: 0.240 AC: 7575 AN: 31530

GnomAD4 genome AF: 0.228 AC: 34617 AN: 151868 Hom.: 5294 Cov.: 31 AF XY: 0.231 AC XY: 17105 AN XY: 74160

African (AFR) AF: 0.0552 AC: 2290 AN: 41482

American (AMR) AF: 0.187 AC: 2858 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1173 AN: 5150

South Asian (SAS) AF: 0.132 AC: 636 AN: 4816

European-Finnish (FIN) AF: 0.454 AC: 4764 AN: 10494

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21640 AN: 67892

Other (OTH) AF: 0.182 AC: 383 AN: 2102

Alfa AF: 0.282 Hom.: 22171

Bravo AF: 0.204

Asia WGS AF: 0.147 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.36
PromoterAI		0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2271893; hg19: chr2-97405440;