2-219208597-C-T

Variant names:

• chr2-219208597-C-T
• rs775086147
• NM_138802.3:c.614C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138802.3(ZFAND2B):​c.614C>T​(p.Ala205Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000483 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: ZFAND2B NM_138802.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.41
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27889222).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138802.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAND2B	NM_138802.3	MANE Select	c.614C>T	p.Ala205Val	missense	Exon 7 of 9	NP_620157.1	Q8WV99-1
	ZFAND2B	NM_001437630.1		c.614C>T	p.Ala205Val	missense	Exon 8 of 9	NP_001424559.1
	ZFAND2B	NM_001437631.1		c.614C>T	p.Ala205Val	missense	Exon 8 of 9	NP_001424560.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAND2B	ENST00000289528.10	TSL:1 MANE Select	c.614C>T	p.Ala205Val	missense	Exon 7 of 9	ENSP00000289528.5	Q8WV99-1
	ZFAND2B	ENST00000409336.5	TSL:5	c.614C>T	p.Ala205Val	missense	Exon 8 of 10	ENSP00000386898.1	Q8WV99-1
	ZFAND2B	ENST00000444522.6	TSL:5	c.614C>T	p.Ala205Val	missense	Exon 8 of 10	ENSP00000411334.3	Q8WV99-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000517 AC: 13 AN: 251266 AF XY: 0.0000516

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000793

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000506 AC: 74 AN: 1461798 Hom.: 0 Cov.: 32 AF XY: 0.0000495 AC XY: 36 AN XY: 727186

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1111936

Other (OTH) AF: 0.000149 AC: 9 AN: 60386

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.40		Loss of phosphorylation at S209 (P = 0.2073)
MVP		0.48
MPC		0.30
ClinPred		0.65	D
GERP RS		5.4
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.63
Mutation Taster		=29/71	disease causing

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

Other links and lift over

dbSNP: rs775086147; hg19: chr2-220073319;