11-65333905-A-G

Position:

• chr11-65333905-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_006268.5(DPF2):​c.19A>G​(p.Asn7Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N7N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DPF2 NM_006268.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.81

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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). GenCC has associacion of gene with Coffin-Siris syndrome 7, Coffin-Siris syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPF2	NM_006268.5	c.19A>G	p.Asn7Asp	missense_variant	1/11	ENST00000528416.6
DPF2	NM_001330308.2	c.19A>G	p.Asn7Asp	missense_variant	1/12
DPF2	XM_017018101.3	c.-719A>G		5_prime_UTR_variant	1/12
DPF2	XR_007062491.1	n.54A>G		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPF2	ENST00000528416.6	c.19A>G	p.Asn7Asp	missense_variant	1/11	1	NM_006268.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

DPF2-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 18, 2023

The DPF2 c.19A>G variant is predicted to result in the amino acid substitution p.Asn7Asp. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;T
Eigen	Benign	0.025
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.55	N;N;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.39	B;.;.
Vest4		0.61
MutPred		0.27		Loss of methylation at K10 (P = 0.07);Loss of methylation at K10 (P = 0.07);Loss of methylation at K10 (P = 0.07);
MVP		0.76
MPC		0.49
ClinPred		0.85	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65101376;