2-97090323-G-A

Position:

• chr2-97090323-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001320848.2(FAHD2B):​c.248C>T​(p.Ala83Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: FAHD2B NM_001320848.2 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47

Genes affected

FAHD2B (HGNC:25318): (fumarylacetoacetate hydrolase domain containing 2B) Predicted to enable hydro-lyase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.117999464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAHD2B	NM_001320848.2	c.248C>T	p.Ala83Val	missense_variant, splice_region_variant	4/9	ENST00000414820.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAHD2B	ENST00000414820.6	c.248C>T	p.Ala83Val	missense_variant, splice_region_variant	4/9	5	NM_001320848.2	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.248C>T (p.A83V) alteration is located in exon 3 (coding exon 2) of the FAHD2B gene. This alteration results from a C to T substitution at nucleotide position 248, causing the alanine (A) at amino acid position 83 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.80	N;N
REVEL	Benign	0.080
Sift	Benign	0.23	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.078	B;B
Vest4		0.16
MutPred		0.46		Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);
MVP		0.29
MPC		1.4
ClinPred		0.50	T
GERP RS		0.60
Varity_R		0.041
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-97756060;