chr2-219208609-C-T

Variant names:

• chr2-219208609-C-T
• rs1950527781
• NM_138802.3:c.626C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138802.3(ZFAND2B):​c.626C>T​(p.Ser209Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 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 2 ACMG points.

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

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.626C>T	p.Ser209Phe	missense	Exon 7 of 9	NP_620157.1	Q8WV99-1
	ZFAND2B	NM_001437630.1		c.626C>T	p.Ser209Phe	missense	Exon 8 of 9	NP_001424559.1
	ZFAND2B	NM_001437631.1		c.626C>T	p.Ser209Phe	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.626C>T	p.Ser209Phe	missense	Exon 7 of 9	ENSP00000289528.5	Q8WV99-1
	ZFAND2B	ENST00000409336.5	TSL:5	c.626C>T	p.Ser209Phe	missense	Exon 8 of 10	ENSP00000386898.1	Q8WV99-1
	ZFAND2B	ENST00000444522.6	TSL:5	c.626C>T	p.Ser209Phe	missense	Exon 8 of 10	ENSP00000411334.3	Q8WV99-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.93
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.42	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.25		Loss of phosphorylation at S209 (P = 0.0398)
MVP		0.78
MPC		0.51
ClinPred		1.0	D
GERP RS		5.0
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.74
gMVP		0.79
Mutation Taster		=28/72	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1950527781; hg19: chr2-220073331;