8-22098192-G-A

Position:

• chr8-22098192-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022749.7(FHIP2B):​c.650G>A​(p.Gly217Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FHIP2B NM_022749.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.175

Genes affected

FHIP2B (HGNC:16492): (FHF complex subunit HOOK interacting protein 2B)

FHIP2B (HGNC:):

ACMG classification

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=0.06720388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIP2B	NM_022749.7	c.650G>A	p.Gly217Glu	missense_variant	6/17	ENST00000289921.8	NP_073586.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIP2B	ENST00000289921.8	c.650G>A	p.Gly217Glu	missense_variant	6/17	5	NM_022749.7	ENSP00000289921.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426416 Hom.: 0 Cov.: 64 AF XY: 0.00000142 AC XY: 1 AN XY: 706266

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.00000832 AC: 1

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

Aug 01, 2024

The c.650G>A (p.G217E) alteration is located in exon 6 (coding exon 6) of the FAM160B2 gene. This alteration results from a G to A substitution at nucleotide position 650, causing the glycine (G) at amino acid position 217 to be replaced by a glutamic acid (E). 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	0.077
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.1
DANN	Benign	0.76
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.76	N
REVEL	Benign	0.043
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.071	B
Vest4		0.25
MVP		0.23
MPC		0.077
ClinPred		0.93	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.015
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs375766097; hg19: chr8-21955703;