Variant 12-61867337-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178539.5(TAFA2):c.89G>T(p.Ser30Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,597,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TAFA2
NM_178539.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.01

Variant links:

Genes affected

TAFA2 (HGNC:21589): (TAFA chemokine like family member 2) This gene is a member of the TAFA family which is composed of five highly homologous genes that encode small secreted proteins. These proteins contain conserved cysteine residues at fixed positions, and are distantly related to MIP-1alpha, a member of the CC-chemokine family. The TAFA proteins are predominantly expressed in specific regions of the brain, and are postulated to function as brain-specific chemokines or neurokines, that act as regulators of immune and nervous cells. [provided by RefSeq, Jul 2008]

TAFA2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062352955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAFA2	NM_178539.5 linkuse as main transcript	c.89G>T	p.Ser30Ile	missense_variant	2/5	ENST00000416284.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAFA2	ENST00000416284.8 linkuse as main transcript	c.89G>T	p.Ser30Ile	missense_variant	2/5	1	NM_178539.5	P1	Q8N3H0-1

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

151080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000330

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:

0.0000821

AC:

AN:

243578

Hom.:

AF XY:

0.0000911

AC XY:

AN XY:

131766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000603

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:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1446600

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

719968

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000512

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000331

AC:

AN:

151166

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73790

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000330

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:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.89G>T (p.S30I) alteration is located in exon 2 (coding exon 1) of the FAM19A2 gene. This alteration results from a G to T substitution at nucleotide position 89, causing the serine (S) at amino acid position 30 to be replaced by an isoleucine (I). 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

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T;.;T;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

0.093

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.0037

MetaRNN

Benign

0.062

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;.;.;.;.

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.3

N;N;D;N;N;N

REVEL

Benign

0.092

Sift

Uncertain

0.029

D;D;D;D;D;D

Sift4G

Uncertain

0.036

D;D;D;.;T;.

Polyphen

0.012

B;B;.;.;.;.

Vest4

0.46

MVP

0.12

MPC

0.70

ClinPred

0.16

GERP RS

4.8

Varity_R

0.33

gMVP

0.49

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