rs2274856

Variant names:

• chr9-13176313-C-A
• rs2274856
• NM_001378778.1:c.2754G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-13176313-C-A
• chr9-13176313-C-T
• chr9-13176313-C-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001378778.1(MPDZ):​c.2754G>T​(p.Ser918Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S918S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MPDZ NM_001378778.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52
• Publications: 21 publications found

Genes affected

MPDZ (HGNC:7208): (multiple PDZ domain crumbs cell polarity complex component) The protein encoded by this gene has multiple PDZ domains, which are hallmarks of protein-protein interactions. The encoded protein is known to interact with the HTR2C receptor and may cause it to clump at the cell surface. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

MPDZ Gene-Disease associations (from GenCC):

• hydrocephalus, nonsyndromic, autosomal recessive 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-13176313-C-A is Benign according to our data. Variant chr9-13176313-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2012008.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.52 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378778.1. 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
	MPDZ	NM_001378778.1	MANE Select	c.2754G>T	p.Ser918Ser	synonymous	Exon 20 of 47	NP_001365707.1	O75970-1
	MPDZ	NM_001375413.1		c.2754G>T	p.Ser918Ser	synonymous	Exon 20 of 48	NP_001362342.1
	MPDZ	NM_001330637.2		c.2754G>T	p.Ser918Ser	synonymous	Exon 20 of 47	NP_001317566.1	O75970-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDZ	ENST00000319217.12	TSL:5 MANE Select	c.2754G>T	p.Ser918Ser	synonymous	Exon 20 of 47	ENSP00000320006.7	O75970-1
	MPDZ	ENST00000541718.5	TSL:1	c.2754G>T	p.Ser918Ser	synonymous	Exon 20 of 46	ENSP00000439807.1	O75970-2
	MPDZ	ENST00000447879.6	TSL:1	c.2754G>T	p.Ser918Ser	synonymous	Exon 20 of 46	ENSP00000415208.1	O75970-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456312 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 723860

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39428

South Asian (SAS) AF: 0.00 AC: 0 AN: 85298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108984

Other (OTH) AF: 0.00 AC: 0 AN: 60174

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.13
DANN	Benign	0.32
PhyloP100		-1.5
PromoterAI		-0.013	Neutral

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: rs2274856; hg19: chr9-13176312;