LDHA p.Lys232Asn

Variant names:

• chr11-18403797-G-T
• NM_005566.4:c.696G>T
• LDHA p.Lys232Asn

Your query was ambiguous. Multiple possible variants found:

• chr11-18403797-G-T
• chr11-18403797-G-C

Variant summary

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

The NM_005566.4(LDHA):​c.696G>T​(p.Lys232Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LDHA NM_005566.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 0 publications found

Genes affected

LDHA (HGNC:6535): (lactate dehydrogenase A) This gene encodes the A subunit of lactate dehydrogenase enzyme which catalyzes the reversible conversion of pyruvate to lactate with the concomitant oxidation of NADH to NAD in anaerobic glycolysis. The protein is found predominantly in skeletal muscle and belongs to the lactate dehydrogenase family. Mutations in this gene have been linked to exertional myoglobinuria. The human genome contains several non-transcribed pseudogenes of this gene. [provided by RefSeq, Sep 2023]

LDHA Gene-Disease associations (from GenCC):

• glycogen storage disease due to lactate dehydrogenase M-subunit deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

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_005566.4. 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
	LDHA	NM_005566.4	MANE Select	c.696G>T	p.Lys232Asn	missense	Exon 6 of 8	NP_005557.1	P00338-1
	LDHA	NM_001165414.2		c.783G>T	p.Lys261Asn	missense	Exon 6 of 8	NP_001158886.1	P00338-3
	LDHA	NM_001135239.2		c.522G>T	p.Lys174Asn	missense	Exon 5 of 7	NP_001128711.1	P00338-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDHA	ENST00000422447.8	TSL:1 MANE Select	c.696G>T	p.Lys232Asn	missense	Exon 6 of 8	ENSP00000395337.3	P00338-1
	LDHA	ENST00000542179.1	TSL:1	c.696G>T	p.Lys232Asn	missense	Exon 5 of 7	ENSP00000445331.1	P00338-1
	LDHA	ENST00000545215.5	TSL:1	n.*440G>T		non_coding_transcript_exon	Exon 5 of 7	ENSP00000442637.1	F5GWW2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	0.0088	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.86	D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.27
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.080	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.90
gMVP		0.85
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-18425344;