10-86942682-A-C

Position:

• chr10-86942682-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024756.3(MMRN2):​c.2102T>G​(p.Leu701Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MMRN2 NM_024756.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.43

Genes affected

MMRN2 (HGNC:19888): (multimerin 2) This gene encodes a protein belonging to the member of elastin microfibril interface-located (EMILIN) protein family. This family member is an extracellular matrix glycoprotein that can interfere with tumor angiogenesis and growth. It serves as a transforming growth factor beta antagonist and can interfere with the VEGF-A/VEGFR2 pathway. A related pseudogene has been identified on chromosome 6. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMRN2	NM_024756.3	c.2102T>G	p.Leu701Arg	missense_variant	6/7	ENST00000372027.10	NP_079032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMRN2	ENST00000372027.10	c.2102T>G	p.Leu701Arg	missense_variant	6/7	1	NM_024756.3	ENSP00000361097	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.2102T>G (p.L701R) alteration is located in exon 6 (coding exon 6) of the MMRN2 gene. This alteration results from a T to G substitution at nucleotide position 2102, causing the leucine (L) at amino acid position 701 to be replaced by an arginine (R). 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	Benign	0.33
BayesDel_addAF	Benign	0.0058	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.021
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.20
Sift	Benign	0.052	T
Sift4G	Uncertain	0.038	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.30		Gain of MoRF binding (P = 0.0367);
MVP		0.32
MPC		2.4
ClinPred		0.93	D
GERP RS		3.4
Varity_R		0.27
gMVP		0.72

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: chr10-88702439;