rs2299851

Variant names:

• chr6-31750825-G-A
• rs2299851
• NM_172166.4:c.813-2476G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 38 publications found

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:41994): (MSH5-SAPCD1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring mutS homolog 5 (MSH5) and chromosome 6 open reading frame 26 (C6orf26) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MSH5	NM_172166.4	c.813-2476G>A		intron_variant	Intron 10 of 24	ENST00000375750.9	NP_751898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH5	ENST00000375750.9	c.813-2476G>A		intron_variant	Intron 10 of 24	1	NM_172166.4	ENSP00000364903.3
MSH5-SAPCD1	ENST00000493662.6	n.864-2476G>A		intron_variant	Intron 10 of 28	1		ENSP00000417871.2

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

African (AFR) AF: 0.0278 AC: 1156 AN: 41524

American (AMR) AF: 0.165 AC: 2517 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3470

East Asian (EAS) AF: 0.149 AC: 769 AN: 5174

South Asian (SAS) AF: 0.132 AC: 635 AN: 4822

European-Finnish (FIN) AF: 0.177 AC: 1867 AN: 10566

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0958 AC: 6511 AN: 67996

Other (OTH) AF: 0.0764 AC: 161 AN: 2108

Alfa AF: 0.0940 Hom.: 3363

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
PhyloP100		-0.010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2299851; hg19: chr6-31718602;