1-78046330-C-G

Variant summary

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

The NM_017655.6(GIPC2):c.236C>G(p.Ser79Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GIPC2 NM_017655.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.41

Genes affected

GIPC2 (HGNC:18177): (GIPC PDZ domain containing family member 2) Enables identical protein binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	UniProt
GIPC2	NM_017655.6	c.236C>G	p.Ser79Trp	missense_variant	1/6	ENST00000370759.4
GIPC2	XM_047423230.1	c.236C>G	p.Ser79Trp	missense_variant	1/6
GIPC2	NM_001304725.2	c.18+1236C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIPC2	ENST00000370759.4	c.236C>G	p.Ser79Trp	missense_variant	1/6	1	NM_017655.6	P1
GIPC2	ENST00000476882.1	n.79-34345C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.236C>G (p.S79W) alteration is located in exon 1 (coding exon 1) of the GIPC2 gene. This alteration results from a C to G substitution at nucleotide position 236, causing the serine (S) at amino acid position 79 to be replaced by a tryptophan (W). 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	0.21
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	0.74	D
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.43		Loss of relative solvent accessibility (P = 0.0414);
MVP		0.87
MPC		0.62
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.49
gMVP		0.46

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: chr1-78512014;