2-96711646-G-A

Variant names:

• chr2-96711646-G-A
• rs80129946
• NM_030805.4:c.784+10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030805.4(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 NM_030805.4 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LMAN2L	NM_030805.4	c.784+10C>T		intron_variant	Intron 6 of 7	ENST00000264963.9	NP_110432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMAN2L	ENST00000264963.9	c.784+10C>T		intron_variant	Intron 6 of 7	1	NM_030805.4	ENSP00000264963.4

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

GnomAD2 exomes AF: 0.00508 AC: 1276 AN: 251174 AF XY: 0.00368

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 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 AC: 2351 AN: 32870

Gnomad4 AMR exome AF: 0.00441 AC: 197 AN: 44692

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25970

Gnomad4 EAS exome AF: 0.000101 AC: 4 AN: 39570

Gnomad4 SAS exome AF: 0.000210 AC: 18 AN: 85750

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53410

Gnomad4 NFE exome AF: 0.0000827 AC: 90 AN: 1088436

Gnomad4 Remaining exome AF: 0.00399 AC: 237 AN: 59448

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 AC: 0.0653272 AN: 0.0653272

Gnomad4 AMR AF: 0.0103 AC: 0.0102574 AN: 0.0102574

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.000385 AC: 0.000385356 AN: 0.000385356

Gnomad4 SAS AF: 0.000414 AC: 0.000414079 AN: 0.000414079

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000191 AC: 0.000191081 AN: 0.000191081

Gnomad4 OTH AF: 0.0161 AC: 0.0160681 AN: 0.0160681

Alfa AF: 0.0150 Hom.: 23

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
Mutation Taster		=100/0	polymorphism (auto)

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;