chr7-76048243-G-T

Variant names:

• chr7-76048243-G-T
• rs189383313
• NM_005918.4:c.66+17G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_005918.4(MDH2):​c.66+17G>T variant causes a intron 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 (★).

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MDH2 NM_005918.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.02
• Publications: 0 publications found

Genes affected

MDH2 (HGNC:6971): (malate dehydrogenase 2) Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the mitochondria and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

STYXL1 (HGNC:18165): (serine/threonine/tyrosine interacting like 1) Enables protein phosphatase binding activity; protein phosphatase inhibitor activity; and pseudophosphatase activity. Involved in several processes, including negative regulation of phosphoprotein phosphatase activity; negative regulation of stress granule assembly; and positive regulation of intrinsic apoptotic signaling pathway. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 7-76048243-G-T is Benign according to our data. Variant chr7-76048243-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2762603.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005918.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDH2	NM_005918.4	MANE Select	c.66+17G>T		intron	N/A	NP_005909.2
	MDH2	NM_001282403.2		c.66+17G>T		intron	N/A	NP_001269332.1
	MDH2	NM_001282404.2		c.-87+17G>T		intron	N/A	NP_001269333.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDH2	ENST00000315758.10	TSL:1 MANE Select	c.66+17G>T		intron	N/A	ENSP00000327070.5
	MDH2	ENST00000490105.1	TSL:3	n.83G>T		non_coding_transcript_exon	Exon 1 of 3
	MDH2	ENST00000432020.2	TSL:2	c.66+17G>T		intron	N/A	ENSP00000408649.2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1378836 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 680016

African (AFR) AF: 0.00 AC: 0 AN: 31224

American (AMR) AF: 0.00 AC: 0 AN: 35516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25038

East Asian (EAS) AF: 0.00 AC: 0 AN: 35546

South Asian (SAS) AF: 0.00 AC: 0 AN: 78962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4402

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076454

Other (OTH) AF: 0.00 AC: 0 AN: 57514

GnomAD4 genome Cov.: 35

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 22, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	9.5
DANN	Benign	0.92
PhyloP100		2.0
PromoterAI		0.074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs189383313; hg19: chr7-75677561;