rs1555031372

Variant names:

• chr11-65345981-G-T
• rs1555031372
• NM_006268.5:c.827G>T
• DPF2 p.Cys276Phe

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_006268.5(DPF2):​c.827G>T​(p.Cys276Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPF2 NM_006268.5 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

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]

DPF2 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Coffin-Siris syndrome 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-65345981-G-T is Pathogenic according to our data. Variant chr11-65345981-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 438643.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006268.5. 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
	DPF2	NM_006268.5	MANE Select	c.827G>T	p.Cys276Phe	missense	Exon 8 of 11	NP_006259.1	Q92785-1
	DPF2	NM_001330308.2		c.869G>T	p.Cys290Phe	missense	Exon 9 of 12	NP_001317237.1	J3KMZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPF2	ENST00000528416.6	TSL:1 MANE Select	c.827G>T	p.Cys276Phe	missense	Exon 8 of 11	ENSP00000436901.1	Q92785-1
	DPF2	ENST00000703424.1		c.1379G>T	p.Cys460Phe	missense	Exon 8 of 11	ENSP00000515295.1	A0A994J6A8
	DPF2	ENST00000703425.1		c.938G>T	p.Cys313Phe	missense	Exon 10 of 13	ENSP00000515296.1	A0A994J426

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Coffin-Siris syndrome 1 (1)
1	-	-	Coffin-Siris syndrome 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.27	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Pathogenic	1.1	D
PhyloP100		10
PROVEAN	Benign	-0.68	N
REVEL	Uncertain	0.53
Sift	Benign	0.38	T
Sift4G	Uncertain	0.038	D
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.96
Mutation Taster		=10/90	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1555031372;

hg19: chr11-65113452;