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

Variant summary

Our verdict is Likely benign. The variant received -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. 13/22 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

Publications

0 publications found

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:

FAM66A (HGNC:30444): (family with sequence similarity 66 member A)

FAM66A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137610.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM86B2	NM_001137610.3	MANE Select	c.614G>A	p.Gly205Asp	missense	Exon 6 of 8	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2		n.431+220G>A		intron	N/A
FAM86B2	NR_148877.2		n.350+220G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM86B2	ENST00000262365.9	TSL:5 MANE Select	c.614G>A	p.Gly205Asp	missense	Exon 6 of 8	ENSP00000262365.4	P0C5J1
FAM86B2	ENST00000942450.1		c.584G>A	p.Gly195Asp	missense	Exon 6 of 8	ENSP00000612509.1
FAM86B2	ENST00000870195.1		c.512G>A	p.Gly171Asp	missense	Exon 5 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes

AF:

0.0000620

AC:

AN:

112898

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0000630

AC:

AN:

142898

AF XY:

0.0000390

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 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

African (AFR)

AF:

0.00

AC:

AN:

22918

American (AMR)

AF:

0.0000293

AC:

AN:

34140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20370

East Asian (EAS)

AF:

0.00

AC:

AN:

34342

South Asian (SAS)

AF:

0.000104

AC:

AN:

67014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3200

European-Non Finnish (NFE)

AF:

0.000167

AC:

130

AN:

777394

Other (OTH)

AF:

0.0000436

AC:

AN:

45908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.0000345

AC:

AN:

28956

American (AMR)

AF:

0.00

AC:

AN:

10272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2708

East Asian (EAS)

AF:

0.00

AC:

AN:

3690

South Asian (SAS)

AF:

0.00

AC:

AN:

3070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000110

AC:

AN:

54528

Other (OTH)

AF:

0.00

AC:

AN:

1442

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000613

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.68

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.76

M_CAP

Benign

0.0055

MetaRNN

Benign

0.42

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

3.7

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.13

Sift

Benign

0.056

Sift4G

Uncertain

0.024

Varity_R

0.40

gMVP

0.59

Mutation Taster

=97/3

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over