chr19-35299741-GC-AA

Variant names:

• chr19-35299741-GC-AA
• rs36055167
• NM_002361.4:c.603_604delGCinsAA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_002361.4(MAG):​c.603_604delGCinsAA​(p.Leu202Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L201L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 25)
• Consequence: MAG NM_002361.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

Genes affected

MAG (HGNC:6783): (myelin associated glycoprotein) The protein encoded by this gene is a type I membrane protein and member of the immunoglobulin superfamily. It is thought to be involved in the process of myelination. It is a lectin that binds to sialylated glycoconjugates and mediates certain myelin-neuron cell-cell interactions. Three alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2010]

MAG Gene-Disease associations (from GenCC):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 75

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

ACMG classification

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

• BP6: Variant 19-35299741-GC-AA is Benign according to our data. Variant chr19-35299741-GC-AA is described in ClinVar as Likely_benign. ClinVar VariationId is 475608.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002361.4. 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
	MAG	NM_002361.4	MANE Select	c.603_604delGCinsAA	p.Leu202Met	missense	N/A	NP_002352.1	P20916-1
	MAG	NM_001199216.2		c.528_529delGCinsAA	p.Leu177Met	missense	N/A	NP_001186145.1	P20916-3
	MAG	NM_080600.3		c.603_604delGCinsAA	p.Leu202Met	missense	N/A	NP_542167.1	P20916-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAG	ENST00000392213.8	TSL:1 MANE Select	c.603_604delGCinsAA	p.Leu202Met	missense	N/A	ENSP00000376048.2	P20916-1
	MAG	ENST00000537831.2	TSL:1	c.528_529delGCinsAA	p.Leu177Met	missense	N/A	ENSP00000440695.1	P20916-3
	MAG	ENST00000361922.8	TSL:1	c.603_604delGCinsAA	p.Leu202Met	missense	N/A	ENSP00000355234.4	P20916-2

Frequencies

GnomAD3 genomes Cov.: 25

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia 75 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs36055167; hg19: chr19-35790644;