NM_138802.3:c.719A>G

Variant names:

• chr2-219209039-A-G
• rs202142737
• NM_138802.3:c.719A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_138802.3(ZFAND2B):​c.719A>G​(p.Gln240Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ZFAND2B NM_138802.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.229
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006985575).
• BP6: Variant 2-219209039-A-G is Benign according to our data. Variant chr2-219209039-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2207606.Status of the report is criteria_provided_single_submitter, 1 stars.

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.719A>G	p.Gln240Arg	missense	Exon 8 of 9	NP_620157.1	Q8WV99-1
	ZFAND2B	NM_001270998.2		c.719A>G	p.Gln240Arg	missense	Exon 9 of 10	NP_001257927.1	Q8WV99-1
	ZFAND2B	NM_001437629.1		c.719A>G	p.Gln240Arg	missense	Exon 9 of 10	NP_001424558.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAND2B	ENST00000289528.10	TSL:1 MANE Select	c.719A>G	p.Gln240Arg	missense	Exon 8 of 9	ENSP00000289528.5	Q8WV99-1
	ZFAND2B	ENST00000409336.5	TSL:5	c.719A>G	p.Gln240Arg	missense	Exon 9 of 10	ENSP00000386898.1	Q8WV99-1
	ZFAND2B	ENST00000444522.6	TSL:5	c.719A>G	p.Gln240Arg	missense	Exon 9 of 10	ENSP00000411334.3	Q8WV99-1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251436 AF XY: 0.00

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727214

African (AFR) AF: 0.000418 AC: 14 AN: 33476

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111968

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74496

African (AFR) AF: 0.000192 AC: 8 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000680

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.064
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.9
DANN	Benign	0.87
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.73	N
PhyloP100		0.23
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.050
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.10
MVP		0.24
MPC		0.12
ClinPred		0.0073	T
GERP RS		0.061
Varity_R		0.034
gMVP		0.21
Mutation Taster		=92/8	polymorphism

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: rs202142737; hg19: chr2-220073761;