2-219207897-A-T

Variant names:

• chr2-219207897-A-T
• rs373368661
• NM_138802.3:c.293A>T

Variant summary

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

The NM_138802.3(ZFAND2B):​c.293A>T​(p.Asn98Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 6.83

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.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND2B	NM_138802.3	c.293A>T	p.Asn98Ile	missense_variant	Exon 4 of 9	ENST00000289528.10	NP_620157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND2B	ENST00000289528.10	c.293A>T	p.Asn98Ile	missense_variant	Exon 4 of 9	1	NM_138802.3	ENSP00000289528.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;.;.;T;T;T;T;T;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D;D;D;.;D;.;D;.;D;D
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.9	M;M;.;M;M;.;.;.;M;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.4	D;D;.;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D;D;.;D;D;D;D;D;D;D;D
Sift4G	Benign	0.068	T;D;D;T;D;D;T;D;D;D;T
Polyphen		0.78, 0.94	.;P;.;.;P;.;.;P;P;.;.
Vest4		0.86
MutPred		0.34		Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);.;Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);
MVP		0.64
MPC		0.62
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.89
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs373368661; hg19: chr2-220072619;