Genetic Variant FAM86B2:p.Arg270Gln (chr8-12427740-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001137610.3(FAM86B2):c.809G>A(p.Arg270Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., cov: 12)

Exomes 𝑓: 0.000026 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.21

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03414327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3 link	c.809G>A	p.Arg270Gln	missense_variant	Exon 7 of 8	ENST00000262365.9	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2 link	n.498G>A		non_coding_transcript_exon_variant	Exon 5 of 6
FAM86B2	NR_148877.2 link	n.417G>A		non_coding_transcript_exon_variant	Exon 4 of 5
FAM86B2	NR_148878.2 link	n.698G>A		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.809G>A	p.Arg270Gln	missense_variant	Exon 7 of 8	5	NM_001137610.3	ENSP00000262365.4		P0C5J1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

88502

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000157

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:

0.0000403

AC:

AN:

148804

Hom.:

AF XY:

0.0000363

AC XY:

AN XY:

82624

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000220

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:

0.000268

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000263

AC:

AN:

989178

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

494152

show subpopulations

Gnomad4 AFR exome

AF:

0.000470

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000330

Gnomad4 SAS exome

AF:

0.0000155

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000535

Gnomad4 OTH exome

AF:

0.0000721

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000903

AC:

AN:

88574

Hom.:

Cov.:

AF XY:

0.0000707

AC XY:

AN XY:

42424

show subpopulations

Gnomad4 AFR

AF:

0.000196

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:

0.00270

ExAC

AF:

0.0000970

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.809G>A (p.R270Q) alteration is located in exon 7 (coding exon 7) of the FAM86B2 gene. This alteration results from a G to A substitution at nucleotide position 809, causing the arginine (R) at amino acid position 270 to be replaced by a glutamine (Q). 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

0.074

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0050

DANN

Benign

0.93

DEOGEN2

Benign

0.0045

T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.58

T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.74

N;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.76

N;.;N

REVEL

Benign

0.031

Sift

Benign

0.65

T;.;T

Sift4G

Benign

0.60

T;T;T

Polyphen

0.014

B;.;.

Vest4

0.078

MVP

0.068

MPC

2.0

ClinPred

0.045

GERP RS

-3.6

Varity_R

0.023

gMVP

0.22

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