2-96711646-G-A

Position:

• chr2-96711646-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000264963.9(LMAN2L):​c.784+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,587,318 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (98 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (99 hom.)
• Consequence: LMAN2L ENST00000264963.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.41

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-96711646-G-A is Benign according to our data. Variant chr2-96711646-G-A is described in ClinVar as [Benign]. Clinvar id is 775745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMAN2L	NM_030805.4	c.784+10C>T		intron_variant		ENST00000264963.9	NP_110432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMAN2L	ENST00000264963.9	c.784+10C>T		intron_variant		1	NM_030805.4	ENSP00000264963	P1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2922 AN: 152222 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0162

GnomAD3 exomes AF: 0.00508 AC: 1276 AN: 251174 Hom.: 39 AF XY: 0.00368 AC XY: 499 AN XY: 135742

Gnomad AFR exome AF: 0.0668

Gnomad AMR exome AF: 0.00358

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00203 AC: 2908 AN: 1434978 Hom.: 99 Cov.: 28 AF XY: 0.00176 AC XY: 1259 AN XY: 715544

Gnomad4 AFR exome AF: 0.0715

Gnomad4 AMR exome AF: 0.00441

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000210

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000827

Gnomad4 OTH exome AF: 0.00399

GnomAD4 genome AF: 0.0192 AC: 2924 AN: 152340 Hom.: 98 Cov.: 32 AF XY: 0.0184 AC XY: 1368 AN XY: 74494

Gnomad4 AFR AF: 0.0653

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0138 Hom.: 19

Bravo AF: 0.0218

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.63
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs80129946; hg19: chr2-97377383;