X-70426398-G-A

Variant names:

• chrX-70426398-G-A
• NM_017711.4:c.391G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017711.4(GDPD2):​c.391G>A​(p.Val131Met) variant causes a missense change involving the alteration of a non-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: 23)
• Consequence: GDPD2 NM_017711.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

Genes affected

GDPD2 (HGNC:25974): (glycerophosphodiester phosphodiesterase domain containing 2) This gene encodes a member of the glycerophosphodiester phosphodiesterase enzyme family. The encoded protein hydrolyzes glycerophosphoinositol to produce inositol 1-phosphate and glycerol. This protein may have a role in osteoblast differentiation and growth. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017711.4. 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
	GDPD2	NM_017711.4	MANE Select	c.391G>A	p.Val131Met	missense	Exon 6 of 16	NP_060181.2
	GDPD2	NM_001171192.2		c.391G>A	p.Val131Met	missense	Exon 6 of 17	NP_001164663.1	Q9HCC8-3
	GDPD2	NM_001171191.2		c.154G>A	p.Val52Met	missense	Exon 4 of 14	NP_001164662.1	Q9HCC8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDPD2	ENST00000374382.4	TSL:1 MANE Select	c.391G>A	p.Val131Met	missense	Exon 6 of 16	ENSP00000363503.3	Q9HCC8-1
	GDPD2	ENST00000453994.6	TSL:2	c.391G>A	p.Val131Met	missense	Exon 6 of 17	ENSP00000414019.2	Q9HCC8-3
	GDPD2	ENST00000913685.1		c.391G>A	p.Val131Met	missense	Exon 6 of 16	ENSP00000583744.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.22
Sift	Uncertain	0.028	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.41
MutPred		0.48		Loss of MoRF binding (P = 0.682)
MVP		0.54
MPC		1.2
ClinPred		0.92	D
GERP RS		4.5
Varity_R		0.16
gMVP		0.54
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chrX-69646248;