2-219208308-A-G

Variant names:

• chr2-219208308-A-G
• NM_138802.3:c.487A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_138802.3(ZFAND2B):​c.487A>G​(p.Ser163Gly) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFAND2B NM_138802.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

Genes affected

ZFAND2B (HGNC:25206): (zinc finger AN1-type containing 2B) This gene encodes a protein containing AN1-type zinc-fingers and ubiquitin-interacting motifs. The encoded protein likely associates with the proteosome to stimulate the degradation of toxic or misfolded proteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity ZFN2B_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11738011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND2B	NM_138802.3	c.487A>G	p.Ser163Gly	missense_variant	Exon 5 of 9	ENST00000289528.10	NP_620157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND2B	ENST00000289528.10	c.487A>G	p.Ser163Gly	missense_variant	Exon 5 of 9	1	NM_138802.3	ENSP00000289528.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.487A>G (p.S163G) alteration is located in exon 5 (coding exon 5) of the ZFAND2B gene. This alteration results from a A to G substitution at nucleotide position 487, causing the serine (S) at amino acid position 163 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	Benign	0.075
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.0088	.;T;.;.;T;T;T;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.73	.;T;T;T;.;T;T;.;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M;.;M;M;.;.;M;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N;.;N;N;N;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.21	T;T;.;T;T;T;T;T;T
Sift4G	Benign	0.27	T;T;T;T;T;T;T;T;T
Polyphen		0.0040, 0.0030	.;B;.;.;B;.;B;B;.
Vest4		0.19
MutPred		0.22		Gain of catalytic residue at S163 (P = 0.0025);Gain of catalytic residue at S163 (P = 0.0025);.;Gain of catalytic residue at S163 (P = 0.0025);Gain of catalytic residue at S163 (P = 0.0025);Gain of catalytic residue at S163 (P = 0.0025);Gain of catalytic residue at S163 (P = 0.0025);Gain of catalytic residue at S163 (P = 0.0025);Gain of catalytic residue at S163 (P = 0.0025);
MVP		0.34
MPC		0.16
ClinPred		0.086	T
GERP RS		2.7
Varity_R		0.081
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-220073030;