Variant chr5-140647376-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002488.5(NDUFA2):c.102-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,611,094 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 1 hom. )

Consequence

NDUFA2
NM_002488.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.117

Variant links:

Genes affected

NDUFA2 (HGNC:7685): (NADH:ubiquinone oxidoreductase subunit A2) The encoded protein is a subunit of the hydrophobic protein fraction of the NADH:ubiquinone oxidoreductase (complex 1), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane, and may be involved in regulating complex I activity or its assembly via assistance in redox processes. Mutations in this gene are associated with Leigh syndrome, an early-onset progressive neurodegenerative disorder. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

NDUFA2 links:

TMCO6 (HGNC:):

TMCO6 links:

IK (HGNC:5958): (IK cytokine) The protein encoded by this gene was identified by its RED repeat, a stretch of repeated arginine, glutamic acid and aspartic acid residues. The protein localizes to discrete dots within the nucleus, excluding the nucleolus. Its function is unknown. This gene maps to chromosome 5; however, a pseudogene may exist on chromosome 2. [provided by RefSeq, Jul 2008]

IK links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 5-140647376-G-A is Benign according to our data. Variant chr5-140647376-G-A is described in ClinVar as [Benign]. Clinvar id is 1965017.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
NDUFA2	NM_002488.5 linkuse as main transcript	c.102-14C>T	splice_polypyrimidine_tract_variant, intron_variant		ENST00000252102.9
TMCO6	XM_047417354.1 linkuse as main transcript	c.*559G>A	3_prime_UTR_variant	11/11
NDUFA2	NM_001185012.2 linkuse as main transcript	c.102-14C>T	splice_polypyrimidine_tract_variant, intron_variant
NDUFA2	NR_033697.2 linkuse as main transcript	n.255C>T	non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA2	ENST00000252102.9 linkuse as main transcript	c.102-14C>T	splice_polypyrimidine_tract_variant, intron_variant		1	NM_002488.5	P1	O43678-1
NDUFA2	ENST00000512088.1 linkuse as main transcript	c.102-14C>T	splice_polypyrimidine_tract_variant, intron_variant		2			O43678-2
IK	ENST00000513256.5 linkuse as main transcript	c.4+67G>A	intron_variant		4
NDUFA2	ENST00000502960.1 linkuse as main transcript	n.396C>T	non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

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:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000759

AC:

AN:

250380

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135336

show subpopulations

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 SAS exome

AF:

0.000623

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1458922

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

725130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000465

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.94

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over