Genetic Variant FAM86B2:p.Ala255Asp (chr8-12427785-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001137610.3(FAM86B2):c.764C>A(p.Ala255Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A255V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 8)

Exomes 𝑓: 0.000012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM86B2
NM_001137610.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09723067).

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.764C>A	p.Ala255Asp	missense	Exon 7 of 8	NP_001131082.1	P0C5J1
FAM86B2	NR_148876.2		n.453C>A		non_coding_transcript_exon	Exon 5 of 6
FAM86B2	NR_148877.2		n.372C>A		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM86B2	ENST00000262365.9	TSL:5 MANE Select	c.764C>A	p.Ala255Asp	missense	Exon 7 of 8	ENSP00000262365.4	P0C5J1
FAM86B2	ENST00000942450.1		c.734C>A	p.Ala245Asp	missense	Exon 7 of 8	ENSP00000612509.1
FAM86B2	ENST00000870195.1		c.662C>A	p.Ala221Asp	missense	Exon 6 of 7	ENSP00000540254.1

Frequencies

GnomAD3 genomes

AF:

0.0000140

AC:

AN:

71334

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000161

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

GnomAD2 exomes

AF:

0.0000959

AC:

AN:

93824

AF XY:

0.0000193

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000596

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000119

AC:

AN:

925464

Hom.:

Cov.:

AF XY:

0.00000645

AC XY:

AN XY:

464992

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24248

American (AMR)

AF:

0.000361

AC:

AN:

30466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15578

East Asian (EAS)

AF:

0.00

AC:

AN:

29556

South Asian (SAS)

AF:

0.00

AC:

AN:

63246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2708

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

694442

Other (OTH)

AF:

0.00

AC:

AN:

39636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000140

AC:

AN:

71334

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20682

American (AMR)

AF:

0.000161

AC:

AN:

6216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1556

East Asian (EAS)

AF:

0.00

AC:

AN:

2676

South Asian (SAS)

AF:

0.00

AC:

AN:

1988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

126

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

33266

Other (OTH)

AF:

0.00

AC:

AN:

826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.82

M_CAP

Benign

0.0040

MetaRNN

Benign

0.097

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

PhyloP100

2.4

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.032

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.020

Polyphen

0.63

Vest4

0.26

MutPred

0.46

Gain of phosphorylation at Y251 (P = 0.1257)

MVP

0.043

MPC

4.3

ClinPred

0.24

GERP RS

-0.26

Varity_R

0.37

gMVP

0.68

Mutation Taster

=96/4

polymorphism

(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

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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