Submissions for variant NM_002454.3(MTRR):c.781-2A>T

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV003388704	SCV004100426	likely pathogenic	Methylcobalamin deficiency type cblE		criteria provided, single submitter	clinical testing	The splice acceptor variant c.781-2A>T in MTRR (NM_002454.3) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.781-2A>T variant is observed in 1/30,612 (0.0033%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant affects an invariant splice nucleotide and hence is predicted to cause protein truncation. For these reasons, this variant has been classified as Likely Pathogenic. No reportable variant in the MTRR gene has been detected in the spouse.
Baylor Genetics	RCV003466073	SCV004198787	uncertain significance	Neural tube defects, folate-sensitive	2022-01-12	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV004577039	SCV005061013	likely pathogenic	Methylcobalamin deficiency type cblG		criteria provided, single submitter	clinical testing	The splice acceptor c.781-2A>T gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.781-2A>T variant is reported with an allele frequency of 0.0004% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has not been reported to the ClinVar database. SpliceAi predicts a acceptor loss of 0.99 & an acceptor gain of 0.57 for this variant, indicating that this variant might strongly affect the consensus splice site. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.