Variant 7-4909975-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000404774.7(MMD2):c.515C>T(p.Ala172Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

MMD2
ENST00000404774.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.733

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052760094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MMD2	NM_198403.4 linkuse as main transcript	c.468-25C>T		intron_variant		ENST00000401401.8	NP_940685.3
MMD2	NM_001100600.2 linkuse as main transcript	c.515C>T	p.Ala172Val	missense_variant	6/7		NP_001094070.1
MMD2	NM_001270375.2 linkuse as main transcript	c.468-25C>T		intron_variant			NP_001257304.1
MMD2	NR_072989.2 linkuse as main transcript	n.739C>T		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMD2	ENST00000404774.7 linkuse as main transcript	c.515C>T	p.Ala172Val	missense_variant	6/7	1		ENSP00000384690		Q8IY49-1
MMD2	ENST00000401401.8 linkuse as main transcript	c.468-25C>T		intron_variant		1	NM_198403.4	ENSP00000384141	P1	Q8IY49-2
MMD2	ENST00000406755.5 linkuse as main transcript	c.468-25C>T		intron_variant		1		ENSP00000385963		Q8IY49-3
MMD2	ENST00000612910.1 linkuse as main transcript	c.468-25C>T		intron_variant		5		ENSP00000484193		Q8IY49-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248276

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134802

show subpopulations

Gnomad AFR exome

AF:

0.0000650

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.000250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000827

AC:

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

Jul 26, 2022

The c.515C>T (p.A172V) alteration is located in exon 6 (coding exon 6) of the MMD2 gene. This alteration results from a C to T substitution at nucleotide position 515, causing the alanine (A) at amino acid position 172 to be replaced by a valine (V). 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

0.082

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.9

DANN

Benign

0.61

DEOGEN2

Benign

0.022

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.38

M_CAP

Benign

0.0074

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.28

REVEL

Benign

0.17

Sift

Benign

0.73

Sift4G

Benign

0.48

Polyphen

0.0010

Vest4

0.22

MVP

0.040

MPC

0.037

ClinPred

0.047

GERP RS

4.4

Varity_R

0.018

gMVP

0.24

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

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