Genetic Variant FAM86B2:p.Arg285Cys (chr8-12427696-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001137610.3(FAM86B2):c.853C>T(p.Arg285Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0087 in 1,000,962 control chromosomes in the GnomAD database, including 2,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R285S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0048 ( 98 hom., cov: 14)

Exomes 𝑓: 0.0087 ( 2421 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.09

Variant links:

Genes affected

FAM86B2 (HGNC:32222): (family with sequence similarity 86 member B2) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

FAM86B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012582749).

BP6

Variant 8-12427696-G-A is Benign according to our data. Variant chr8-12427696-G-A is described in ClinVar as [Benign]. Clinvar id is 2658432.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2421 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3 link	c.853C>T	p.Arg285Cys	missense_variant	Exon 7 of 8	ENST00000262365.9	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2 link	n.542C>T		non_coding_transcript_exon_variant	Exon 5 of 6
FAM86B2	NR_148877.2 link	n.461C>T		non_coding_transcript_exon_variant	Exon 4 of 5
FAM86B2	NR_148878.2 link	n.742C>T		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B2	ENST00000262365.9 link	c.853C>T	p.Arg285Cys	missense_variant	Exon 7 of 8	5	NM_001137610.3	ENSP00000262365.4		P0C5J1

Frequencies

GnomAD3 genomes

AF:

0.00483

AC:

470

AN:

97218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00277

Gnomad ASJ

AF:

0.00297

Gnomad EAS

AF:

0.000274

Gnomad SAS

AF:

0.000334

Gnomad FIN

AF:

0.00347

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00847

Gnomad OTH

AF:

0.00566

GnomAD3 exomes

AF:

0.00523

AC:

881

AN:

168394

Hom.:

241

AF XY:

0.00501

AC XY:

464

AN XY:

92584

show subpopulations

Gnomad AFR exome

AF:

0.00180

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00100

Gnomad EAS exome

AF:

0.000276

Gnomad SAS exome

AF:

0.00104

Gnomad FIN exome

AF:

0.00472

Gnomad NFE exome

AF:

0.00981

Gnomad OTH exome

AF:

0.00410

GnomAD4 exome

AF:

0.00870

AC:

8704

AN:

1000962

Hom.:

2421

Cov.:

AF XY:

0.00856

AC XY:

4275

AN XY:

499408

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00132

Gnomad4 EAS exome

AF:

0.000164

Gnomad4 SAS exome

AF:

0.000867

Gnomad4 FIN exome

AF:

0.00641

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00458

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00483

AC:

470

AN:

97302

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

188

AN XY:

47050

show subpopulations

Gnomad4 AFR

AF:

0.00146

Gnomad4 AMR

AF:

0.00277

Gnomad4 ASJ

AF:

0.00297

Gnomad4 EAS

AF:

0.000275

Gnomad4 SAS

AF:

0.000335

Gnomad4 FIN

AF:

0.00347

Gnomad4 NFE

AF:

0.00848

Gnomad4 OTH

AF:

0.00556

ExAC

AF:

0.00606

AC:

536

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAM86B2: PP2, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

T;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

-0.081

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.84

T;T;D

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Pathogenic

4.0

H;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-6.2

D;.;D

REVEL

Benign

0.20

Sift

Uncertain

0.014

D;.;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.97

D;.;.

Vest4

0.53

MVP

0.36

MPC

2.2

ClinPred

0.091

GERP RS

1.8

Varity_R

0.63

gMVP

0.86

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