Variant 7-4925519-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198403.4(MMD2):c.61C>G(p.Arg21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000703 in 1,421,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

MMD2
NM_198403.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Variant links:

Genes affected

MMD2 (HGNC:30133): (monocyte to macrophage differentiation associated 2) This gene encodes a member of the PAQR (progestin and adipoQ receptor) family. Members of this family are evolutionarily conserved with significant sequence identity to bacterial hemolysin-like proteins and are defined by a set of seven transmembrane domains. The protein encoded by this gene localizes to the Golgi apparatus to modulate Ras signaling. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]

MMD2 links:

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ACMG classification

Classification made for transcript

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
MMD2	NM_198403.4 linkuse as main transcript	c.61C>G	p.Arg21Gly	missense_variant	2/7	ENST00000401401.8	NP_940685.3
MMD2	NM_001100600.2 linkuse as main transcript	c.61C>G	p.Arg21Gly	missense_variant	2/7		NP_001094070.1
MMD2	NM_001270375.2 linkuse as main transcript	c.61C>G	p.Arg21Gly	missense_variant	2/8		NP_001257304.1
MMD2	NR_072989.2 linkuse as main transcript	n.231C>G		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMD2	ENST00000401401.8 linkuse as main transcript	c.61C>G	p.Arg21Gly	missense_variant	2/7	1	NM_198403.4	ENSP00000384141	P1	Q8IY49-2
MMD2	ENST00000404774.7 linkuse as main transcript	c.61C>G	p.Arg21Gly	missense_variant	2/7	1		ENSP00000384690		Q8IY49-1
MMD2	ENST00000406755.5 linkuse as main transcript	c.61C>G	p.Arg21Gly	missense_variant	2/8	1		ENSP00000385963		Q8IY49-3
MMD2	ENST00000612910.1 linkuse as main transcript	c.61C>G	p.Arg21Gly	missense_variant	2/7	5		ENSP00000484193		Q8IY49-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000703

AC:

AN:

1421516

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707432

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000492

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000551

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.61C>G (p.R21G) alteration is located in exon 2 (coding exon 2) of the MMD2 gene. This alteration results from a C to G substitution at nucleotide position 61, causing the arginine (R) at amino acid position 21 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

0.61

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;T;.;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

.;D;D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Uncertain

-0.23

MutationAssessor

Pathogenic

3.0

M;M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-4.9

D;D;D;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.012

D;D;D;.

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0, 1.0

.;D;D;.

Vest4

0.76

MutPred

0.46

Loss of MoRF binding (P = 0.0538);Loss of MoRF binding (P = 0.0538);Loss of MoRF binding (P = 0.0538);Loss of MoRF binding (P = 0.0538);

MVP

0.47

MPC

0.28

ClinPred

0.99

GERP RS

2.8

Varity_R

0.41

gMVP

0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over