rs2299851

Positions:

• chr6-31750825-G-A
• chr6-31750825-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172166.4(MSH5):​c.813-2476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 152,148 control chromosomes in the GnomAD database, including 818 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.091 (818 hom., cov: 32)
• Consequence: MSH5 NM_172166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

Genes affected

MSH5 (HGNC:7328): (mutS homolog 5) This gene encodes a member of the mutS family of proteins that are involved in DNA mismatch repair and meiotic recombination. This protein is similar to a Saccharomyces cerevisiae protein that participates in segregation fidelity and crossing-over events during meiosis. This protein plays a role in promoting ionizing radiation-induced apoptosis. This protein forms hetero-oligomers with another member of this family, mutS homolog 4. Polymorphisms in this gene have been linked to various human diseases, including IgA deficiency, common variable immunodeficiency, and premature ovarian failure. Alternative splicing results multiple transcript variants. Read-through transcription also exists between this gene and the downstream chromosome 6 open reading frame 26 (C6orf26) gene. [provided by RefSeq, Feb 2011]

MSH5-SAPCD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH5	NM_172166.4	c.813-2476G>A		intron_variant		ENST00000375750.9
MSH5-SAPCD1	NR_037846.1	n.992-2476G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH5	ENST00000375750.9	c.813-2476G>A		intron_variant		1	NM_172166.4	A2

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13814 AN: 152030 Hom.: 815 Cov.: 32

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.0767

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

GnomAD4 genome AF: 0.0909 AC: 13826 AN: 152148 Hom.: 818 Cov.: 32 AF XY: 0.0975 AC XY: 7250 AN XY: 74366

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.0958

Gnomad4 OTH AF: 0.0764

Alfa AF: 0.0912 Hom.: 1226

Bravo AF: 0.0866

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs2299851; hg19: chr6-31718602;