2-219208291-C-G

Variant names:

• chr2-219208291-C-G
• NM_138802.3:c.470C>G

Variant summary

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

The NM_138802.3(ZFAND2B):​c.470C>G​(p.Ser157Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFAND2B NM_138802.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15078023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND2B	NM_138802.3	c.470C>G	p.Ser157Cys	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.470C>G	p.Ser157Cys	missense_variant	Exon 5 of 9	1	NM_138802.3	ENSP00000289528.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.10	.;T;.;.;T;T;T;T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.61	.;T;T;T;.;T;T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L;L;.;L;L;.;.;L;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.4	N;N;.;N;N;N;N;N;N
REVEL	Benign	0.041
Sift	Uncertain	0.0070	D;D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.051	T;T;T;T;T;D;D;T;T
Polyphen		0.93, 0.037	.;P;.;.;P;.;B;P;.
Vest4		0.17
MutPred		0.31		Loss of glycosylation at S157 (P = 0.003);Loss of glycosylation at S157 (P = 0.003);.;Loss of glycosylation at S157 (P = 0.003);Loss of glycosylation at S157 (P = 0.003);Loss of glycosylation at S157 (P = 0.003);Loss of glycosylation at S157 (P = 0.003);Loss of glycosylation at S157 (P = 0.003);Loss of glycosylation at S157 (P = 0.003);
MVP		0.51
MPC		0.24
ClinPred		0.40	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-220073013;