rs112167630

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001271938.2(MEGF8):c.7054G>A(p.Val2352Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 1,581,696 control chromosomes in the GnomAD database, including 500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 31 hom., cov: 27)

Exomes 𝑓: 0.024 ( 469 hom. )

Consequence

MEGF8
NM_001271938.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.54

Publications

9 publications found

Variant links:

Genes affected

MEGF8 (HGNC:3233): (multiple EGF like domains 8) The protein encoded by this gene is a single-pass type I membrane protein of unknown function that contains several EGF-like domains, Kelch repeats, and PSI domains. Defects in this gene are a cause of Carpenter syndrome 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

MEGF8 Gene-Disease associations (from GenCC):

MEGF8-related Carpenter syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
Carpenter syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MEGF8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008328646).

BP6

Variant 19-42370749-G-A is Benign according to our data. Variant chr19-42370749-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 473343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0163 (2454/150866) while in subpopulation NFE AF = 0.0246 (1662/67610). AF 95% confidence interval is 0.0236. There are 31 homozygotes in GnomAd4. There are 1177 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF8	NM_001271938.2 link	c.7054G>A	p.Val2352Met	missense_variant	Exon 40 of 42	ENST00000251268.11	NP_001258867.1	Q7Z7M0-1
MEGF8	NM_001410.3 link	c.6853G>A	p.Val2285Met	missense_variant	Exon 39 of 41		NP_001401.2	Q7Z7M0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEGF8	ENST00000251268.11 link	c.7054G>A	p.Val2352Met	missense_variant	Exon 40 of 42	5	NM_001271938.2	ENSP00000251268.5		Q7Z7M0-1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2455

AN:

150752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00411

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.00640

Gnomad ASJ

AF:

0.0309

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00189

Gnomad FIN

AF:

0.0341

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0165

GnomAD2 exomes

AF:

0.0179

AC:

3632

AN:

202642

AF XY:

0.0182

show subpopulations

Gnomad AFR exome

AF:

0.00316

Gnomad AMR exome

AF:

0.00538

Gnomad ASJ exome

AF:

0.0326

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0362

Gnomad NFE exome

AF:

0.0261

Gnomad OTH exome

AF:

0.0208

GnomAD4 exome

AF:

0.0235

AC:

33649

AN:

1430830

Hom.:

469

Cov.:

AF XY:

0.0228

AC XY:

16184

AN XY:

708736

show subpopulations

African (AFR)

AF:

0.00338

AC:

111

AN:

32830

American (AMR)

AF:

0.00567

AC:

226

AN:

39840

Ashkenazi Jewish (ASJ)

AF:

0.0352

AC:

900

AN:

25566

East Asian (EAS)

AF:

0.00

AC:

AN:

38222

South Asian (SAS)

AF:

0.00212

AC:

173

AN:

81674

European-Finnish (FIN)

AF:

0.0359

AC:

1846

AN:

51414

Middle Eastern (MID)

AF:

0.00279

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.0267

AC:

29265

AN:

1096214

Other (OTH)

AF:

0.0187

AC:

1112

AN:

59340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1436

2873

4309

5746

7182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0163

AC:

2454

AN:

150866

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1177

AN XY:

73644

show subpopulations

African (AFR)

AF:

0.00410

AC:

169

AN:

41216

American (AMR)

AF:

0.00645

AC:

AN:

15028

Ashkenazi Jewish (ASJ)

AF:

0.0309

AC:

107

AN:

3462

East Asian (EAS)

AF:

0.000196

AC:

AN:

5110

South Asian (SAS)

AF:

0.00189

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.0341

AC:

354

AN:

10392

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0246

AC:

1662

AN:

67610

Other (OTH)

AF:

0.0163

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

110

219

329

438

548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0217

Hom.:

126

Bravo

AF:

0.0142

TwinsUK

AF:

0.0270

AC:

100

ALSPAC

AF:

0.0288

AC:

111

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.0248

AC:

213

ExAC

AF:

0.0161

AC:

1944

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 21, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

MEGF8-related Carpenter syndrome

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;T;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.2

.;M;.

PhyloP100

7.5

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.4

N;N;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.0060

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.42

MPC

1.5

ClinPred

0.0086

GERP RS

4.9

Varity_R

0.30

gMVP

0.55

Mutation Taster

=228/72

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs112167630

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over