11-557907-G-C

Variant names:

• chr11-557907-G-C
• NM_173573.3:c.532C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173573.3(LMNTD2):​c.532C>G​(p.Arg178Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LMNTD2 NM_173573.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.384

Genes affected

LMNTD2 (HGNC:28561): (lamin tail domain containing 2) Predicted to be a structural constituent of chromatin. Predicted to be involved in regulation of chromatin assembly. Predicted to act upstream of or within positive regulation of mRNA splicing, via spliceosome. Predicted to be active in lamin filament. [provided by Alliance of Genome Resources, Apr 2022]

LMNTD2-AS1 (HGNC:41204): (LMNTD2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30051082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNTD2	NM_173573.3	c.532C>G	p.Arg178Gly	missense_variant	Exon 5 of 14	ENST00000329451.8	NP_775844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNTD2	ENST00000329451.8	c.532C>G	p.Arg178Gly	missense_variant	Exon 5 of 14	1	NM_173573.3	ENSP00000331167.3
LMNTD2	ENST00000441853.5	c.553C>G	p.Arg185Gly	missense_variant	Exon 6 of 9	3		ENSP00000393529.1
LMNTD2	ENST00000486629.1	c.562C>G	p.Arg188Gly	missense_variant	Exon 5 of 7	5		ENSP00000435529.1
LMNTD2-AS1	ENST00000527620.5	n.313G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.532C>G (p.R178G) alteration is located in exon 5 (coding exon 5) of the LMNTD2 gene. This alteration results from a C to G substitution at nucleotide position 532, causing the arginine (R) at amino acid position 178 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.99	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.011	D;D;.
Polyphen		0.99	D;.;.
Vest4		0.39
MutPred		0.58		Loss of MoRF binding (P = 0.0142);.;.;
MVP		0.23
MPC		0.29
ClinPred		0.97	D
GERP RS		-0.83
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Varity_R		0.13
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-557907;