X-70429940-G-A

Variant names:

• chrX-70429940-G-A
• rs1602840302
• NM_017711.4:c.1184G>A

Variant summary

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

The NM_017711.4(GDPD2):​c.1184G>A​(p.Arg395Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,366 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: GDPD2 NM_017711.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.46
• 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]

ENSG00000284391 (HGNC:):

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.1184G>A	p.Arg395Gln	missense	Exon 12 of 16	NP_060181.2
	GDPD2	NM_001171192.2		c.1184G>A	p.Arg395Gln	missense	Exon 12 of 17	NP_001164663.1	Q9HCC8-3
	GDPD2	NM_001171191.2		c.947G>A	p.Arg316Gln	missense	Exon 10 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.1184G>A	p.Arg395Gln	missense	Exon 12 of 16	ENSP00000363503.3	Q9HCC8-1
	GDPD2	ENST00000453994.6	TSL:2	c.1184G>A	p.Arg395Gln	missense	Exon 12 of 17	ENSP00000414019.2	Q9HCC8-3
	GDPD2	ENST00000913685.1		c.1184G>A	p.Arg395Gln	missense	Exon 12 of 16	ENSP00000583744.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097366 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1 AN XY: 362724

African (AFR) AF: 0.00 AC: 0 AN: 26395

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19380

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54115

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841333

Other (OTH) AF: 0.00 AC: 0 AN: 46071

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	Uncertain	0.35
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		6.5
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.55
MutPred		0.59		Loss of MoRF binding (P = 0.0591)
MVP		0.32
MPC		1.4
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.80
gMVP		0.87
Mutation Taster		=68/32	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

dbSNP: rs1602840302; hg19: chrX-69649790;