Genetic Variant FAM86B2:p.Gly205Asp (chr8-12428761-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001137610.3(FAM86B2):c.614G>A(p.Gly205Asp) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., cov: 18)

Exomes 𝑓: 0.00013 ( 33 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.41876847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM86B2	NM_001137610.3 link	c.614G>A	p.Gly205Asp	missense_variant	Exon 6 of 8	ENST00000262365.9	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2 link	n.431+220G>A		intron_variant	Intron 4 of 5
FAM86B2	NR_148877.2 link	n.350+220G>A		intron_variant	Intron 3 of 4
FAM86B2	NR_148878.2 link	n.631+220G>A		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM86B2	ENST00000262365.9 link	c.614G>A	p.Gly205Asp	missense_variant	Exon 6 of 8	5	NM_001137610.3	ENSP00000262365.4		P0C5J1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

112898

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000345

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:

0.000110

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000630

AC:

AN:

142898

Hom.:

AF XY:

0.0000390

AC XY:

AN XY:

76858

show subpopulations

Gnomad AFR exome

AF:

0.000122

Gnomad AMR exome

AF:

0.0000476

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:

0.000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000134

AC:

140

AN:

1044030

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

AN XY:

525430

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000293

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.0000436

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000620

AC:

AN:

112898

Hom.:

Cov.:

AF XY:

0.0000187

AC XY:

AN XY:

53528

show subpopulations

Gnomad4 AFR

AF:

0.0000345

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:

0.000110

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000613

Hom.:

ExAC

AF:

0.0000579

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.614G>A (p.G205D) alteration is located in exon 6 (coding exon 6) of the FAM86B2 gene. This alteration results from a G to A substitution at nucleotide position 614, causing the glycine (G) at amino acid position 205 to be replaced by an aspartic acid (D). 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

0.12

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.68

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Benign

0.13

Sift

Benign

0.056

T;D

Sift4G

Uncertain

0.024

D;D

Polyphen

0.097

B;.

Vest4

0.32

MutPred

0.76

Loss of catalytic residue at G205 (P = 0.0397);.;

MVP

0.13

MPC

2.2

ClinPred

0.10

GERP RS

0.22

Varity_R

0.40

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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