chr11-65340429-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_006268.5(DPF2):ā€‹c.77A>Gā€‹(p.Asn26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000021 ( 0 hom. )

Consequence

DPF2
NM_006268.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.60
Variant links:
Genes affected
DPF2 (HGNC:9964): (double PHD fingers 2) The protein encoded by this gene is a member of the d4 domain family, characterized by a zinc finger-like structural motif. This protein functions as a transcription factor which is necessary for the apoptotic response following deprivation of survival factors. It likely serves a regulatory role in rapid hematopoietic cell growth and turnover. This gene is considered a candidate gene for multiple endocrine neoplasia type I, an inherited cancer syndrome involving multiple parathyroid, enteropancreatic, and pituitary tumors. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DPF2. . Gene score misZ: 2.8982 (greater than the threshold 3.09). Trascript score misZ: 3.3532 (greater than threshold 3.09). The gene has 11 curated pathogenic missense variants (we use a threshold of 10). The gene has 23 curated benign missense variants. GenCC has associacion of the gene with Coffin-Siris syndrome 7, Coffin-Siris syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.08024767).
BS2
High AC in GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DPF2NM_006268.5 linkc.77A>G p.Asn26Ser missense_variant 2/11 ENST00000528416.6 NP_006259.1 Q92785-1A0A024R582
DPF2NM_001330308.2 linkc.77A>G p.Asn26Ser missense_variant 2/12 NP_001317237.1 J3KMZ8
DPF2XM_017018101.3 linkc.17A>G p.Asn6Ser missense_variant 2/12 XP_016873590.1
DPF2XR_007062491.1 linkn.112A>G non_coding_transcript_exon_variant 2/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DPF2ENST00000528416.6 linkc.77A>G p.Asn26Ser missense_variant 2/111 NM_006268.5 ENSP00000436901.1 Q92785-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251360
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135832
show subpopulations
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 SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
727248
show subpopulations
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:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000234
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 05, 2024The c.77A>G (p.N26S) alteration is located in exon 2 (coding exon 2) of the DPF2 gene. This alteration results from a A to G substitution at nucleotide position 77, causing the asparagine (N) at amino acid position 26 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 07, 2024This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 26 of the DPF2 protein (p.Asn26Ser). This variant is present in population databases (rs745602444, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DPF2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.048
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
14
DANN
Benign
0.50
DEOGEN2
Benign
0.045
T;.;T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.36
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.080
T;T;T
MetaSVM
Benign
-0.66
T
MutationAssessor
Benign
-1.3
N;N;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.21
N;N;N
REVEL
Benign
0.19
Sift
Benign
1.0
T;T;T
Sift4G
Benign
0.96
T;T;T
Polyphen
0.019
B;.;.
Vest4
0.23
MutPred
0.21
Gain of disorder (P = 0.1399);Gain of disorder (P = 0.1399);Gain of disorder (P = 0.1399);
MVP
0.66
MPC
0.34
ClinPred
0.11
T
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.4
Varity_R
0.046
gMVP
0.11

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs745602444; hg19: chr11-65107900; API