Variant 7-4907403-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 ENST00000401401.8(MMD2):c.734C>G(p.Ser245Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MMD2
ENST00000401401.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22

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:

MMD2 (HGNC:):

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	UniProt
MMD2	NM_198403.4 linkuse as main transcript	c.734C>G	p.Ser245Cys	missense_variant	7/7	ENST00000401401.8	NP_940685.3	Q8IY49-2
MMD2	NM_001100600.2 linkuse as main transcript	c.806C>G	p.Ser269Cys	missense_variant	7/7		NP_001094070.1	Q8IY49-1
MMD2	NM_001270375.2 linkuse as main transcript	c.*202C>G		3_prime_UTR_variant	8/8		NP_001257304.1	Q8IY49-3
MMD2	NR_072989.2 linkuse as main transcript	n.991+39C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MMD2	ENST00000401401.8 linkuse as main transcript	c.734C>G	p.Ser245Cys	missense_variant	7/7	1	NM_198403.4	ENSP00000384141.3	Q8IY49-2
MMD2	ENST00000404774.7 linkuse as main transcript	c.806C>G	p.Ser269Cys	missense_variant	7/7	1		ENSP00000384690.3	Q8IY49-1
MMD2	ENST00000406755.5 linkuse as main transcript	c.*202C>G		3_prime_UTR_variant	8/8	1		ENSP00000385963.1	Q8IY49-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461420

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726972

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Dec 11, 2023

The c.806C>G (p.S269C) alteration is located in exon 7 (coding exon 7) of the MMD2 gene. This alteration results from a C to G substitution at nucleotide position 806, causing the serine (S) at amino acid position 269 to be replaced by a cysteine (C). 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

0.090

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.14

MutPred

0.25

Gain of methylation at K270 (P = 0.0064);.;

MVP

0.13

MPC

0.25

ClinPred

0.95

GERP RS

5.4

Varity_R

0.21

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.35

Position offset: 5

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