Genetic Variant TAFA2:p.Asp112Gly (chr12-61753671-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_178539.5(TAFA2):c.335A>G(p.Asp112Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,612,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

TAFA2
NM_178539.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.86

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA2	NM_178539.5 link	c.335A>G	p.Asp112Gly	missense_variant	Exon 4 of 5	ENST00000416284.8	NP_848634.1	Q8N3H0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA2	ENST00000416284.8 link	c.335A>G	p.Asp112Gly	missense_variant	Exon 4 of 5	1	NM_178539.5	ENSP00000393987.3		Q8N3H0-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000559

AC:

AN:

250548

AF XY:

0.0000369

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1460448

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

726506

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33404

American (AMR)

AF:

0.00

AC:

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

86186

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000199

AC:

221

AN:

1111122

Other (OTH)

AF:

0.000381

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000112

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.0000656

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000123

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.000238

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.335A>G (p.D112G) alteration is located in exon 4 (coding exon 3) of the FAM19A2 gene. This alteration results from a A to G substitution at nucleotide position 335, causing the aspartic acid (D) at amino acid position 112 to be replaced by a glycine (G). 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

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.37

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

.;D;D

M_CAP

Benign

0.037

MetaRNN

Pathogenic

0.86

D;D;D

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.6

M;M;.

PhyloP100

7.9

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-6.6

D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.012

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.89

MVP

0.56

MPC

1.8

ClinPred

0.89

GERP RS

4.6

Varity_R

0.71

gMVP

0.83

Mutation Taster

=35/65

disease causing

(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

Publications

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chr12-61753671-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over