X-70426693-C-T

Variant names:

• chrX-70426693-C-T
• rs767700057
• NM_017711.4:c.508C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017711.4(GDPD2):​c.508C>T​(p.Leu170Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,207,924 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L170I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 2 hem.)
• Consequence: GDPD2 NM_017711.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06164795).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

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.508C>T	p.Leu170Phe	missense	Exon 7 of 16	NP_060181.2
	GDPD2	NM_001171192.2		c.508C>T	p.Leu170Phe	missense	Exon 7 of 17	NP_001164663.1	Q9HCC8-3
	GDPD2	NM_001171191.2		c.271C>T	p.Leu91Phe	missense	Exon 5 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.508C>T	p.Leu170Phe	missense	Exon 7 of 16	ENSP00000363503.3	Q9HCC8-1
	GDPD2	ENST00000453994.6	TSL:2	c.508C>T	p.Leu170Phe	missense	Exon 7 of 17	ENSP00000414019.2	Q9HCC8-3
	GDPD2	ENST00000913685.1		c.508C>T	p.Leu170Phe	missense	Exon 7 of 16	ENSP00000583744.1

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 AN: 111986 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000376

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000553 AC: 1 AN: 180920 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1095938 Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 2 AN XY: 361350

African (AFR) AF: 0.00 AC: 0 AN: 26382

American (AMR) AF: 0.00 AC: 0 AN: 35159

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19357

East Asian (EAS) AF: 0.00 AC: 0 AN: 30192

South Asian (SAS) AF: 0.0000556 AC: 3 AN: 53942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840263

Other (OTH) AF: 0.00 AC: 0 AN: 46024

GnomAD4 genome AF: 0.00000893 AC: 1 AN: 111986 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34142

African (AFR) AF: 0.00 AC: 0 AN: 30786

American (AMR) AF: 0.00 AC: 0 AN: 10673

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.000376 AC: 1 AN: 2659

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6161

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53073

Other (OTH) AF: 0.00 AC: 0 AN: 1512

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.38
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.082
Sift	Benign	0.15	T
Sift4G	Uncertain	0.042	D
Polyphen		0.020	B
Vest4		0.072
MutPred		0.25		Gain of catalytic residue at L170 (P = 0.0805)
MVP		0.59
MPC		0.53
ClinPred		0.14	T
GERP RS		1.1
Varity_R		0.12
gMVP		0.70
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs767700057; hg19: chrX-69646543;