rs768796069

Variant names:

• chr10-87190645-C-T
• rs768796069
• NM_001330112.2:c.2677C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-87190645-C-T
• chr10-87190645-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001330112.2(SHLD2):​c.2677C>T​(p.Pro893Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,611,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: SHLD2 NM_001330112.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03
• Publications: 1 publications found

Genes affected

SHLD2 (HGNC:28773): (shieldin complex subunit 2) Involved in negative regulation of double-strand break repair via homologous recombination; positive regulation of double-strand break repair via nonhomologous end joining; and positive regulation of isotype switching. Located in nucleus and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

NUTM2A-AS1 (HGNC:45161): (NUTM2A antisense RNA 1)

LOC105378410 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027546734).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330112.2. 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
	SHLD2	NM_001330112.2	MANE Select	c.2677C>T	p.Pro893Ser	missense	Exon 10 of 10	NP_001317041.1	Q86V20-2
	SHLD2	NM_001377161.1		c.2626C>T	p.Pro876Ser	missense	Exon 10 of 10	NP_001364090.1
	SHLD2	NM_001377160.1		c.2614C>T	p.Pro872Ser	missense	Exon 10 of 10	NP_001364089.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHLD2	ENST00000298786.5	TSL:5 MANE Select	c.2677C>T	p.Pro893Ser	missense	Exon 10 of 10	ENSP00000298786.3	Q86V20-2
	SHLD2	ENST00000898042.1		c.2821C>T	p.Pro941Ser	missense	Exon 12 of 12	ENSP00000568101.1
	SHLD2	ENST00000898054.1		c.2821C>T	p.Pro941Ser	missense	Exon 11 of 11	ENSP00000568113.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000123 AC: 31 AN: 251064 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000897

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000240 AC: 35 AN: 1459662 Hom.: 0 Cov.: 32 AF XY: 0.0000207 AC XY: 15 AN XY: 726138

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.000783 AC: 35 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111804

Other (OTH) AF: 0.00 AC: 0 AN: 60206

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.000123 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.98	T
PhyloP100		2.0
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.065
Sift	Benign	0.12	T
Sift4G	Benign	0.13	T
Polyphen		0.31	B
Vest4		0.22
MutPred		0.41		Gain of helix (P = 0.0078)
MVP		0.24
MPC		0.61
ClinPred		0.23	T
GERP RS		0.26
Varity_R		0.063
gMVP		0.30
Mutation Taster		=98/2	polymorphism

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: rs768796069; hg19: chr10-88950402;