2-188587887-C-G

Variant names:

• chr2-188587887-C-G
• NM_016315.4:c.781C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016315.4(GULP1):​c.781C>G​(p.Pro261Ala) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GULP1 NM_016315.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

Genes affected

GULP1 (HGNC:18649): (GULP PTB domain containing engulfment adaptor 1) The protein encoded by this gene is an adapter protein necessary for the engulfment of apoptotic cells by phagocytes. Several transcript variants, some protein coding and some thought not to be protein coding, have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GULP1	NM_016315.4	c.781C>G	p.Pro261Ala	missense_variant	Exon 11 of 12	ENST00000409830.6	NP_057399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GULP1	ENST00000409830.6	c.781C>G	p.Pro261Ala	missense_variant	Exon 11 of 12	1	NM_016315.4	ENSP00000386732.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.781C>G (p.P261A) alteration is located in exon 11 (coding exon 9) of the GULP1 gene. This alteration results from a C to G substitution at nucleotide position 781, causing the proline (P) at amino acid position 261 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	.;T;.;T;T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;.;D;.;.;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.63	N;N;.;N;N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D;D
REVEL	Benign	0.27
Sift	Benign	0.18	T;T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T;T
Polyphen		1.0	.;D;.;D;D;D
Vest4		0.73
MutPred		0.34		Loss of disorder (P = 0.063);Loss of disorder (P = 0.063);.;Loss of disorder (P = 0.063);Loss of disorder (P = 0.063);Loss of disorder (P = 0.063);
MVP		0.35
MPC		0.72
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.19
gMVP		0.49

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: chr2-189452614;